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Propionic acidaemia is a rare genetic disease characterised by incomplete metabolism of certain amino acids and, to a lesser degree, fats and cholesterol. The processing error causes propionic acid and other toxic substances to accumulate in the blood. Left untreated, these toxins damage the body’s organs especially the brain.
Propionic acidaemia varies in severity. Some individuals show only mild symptoms, while in others life-threatening complications such as stroke and coma occur. Progressive brain damage is a characteristic feature.
The amino acids that cause a problem in propionic acidaemia are isoleucine, valine, threonine and methionine. Amino acids are the building blocks of proteins. After eating proteins, the body ‘metabolises’ or breaks them down into amino acids. Animal proteins include dairy products, meat, eggs and fish. Proteins are also found in plants including soy, legumes, grains and nuts. The body uses the amino acids to make its own proteins essential for life – for example enzymes; structural proteins in muscles, hair, skin, cells and cartilage; proteins that generate movement in muscles; or those involved in cell functioning or immune responses. In periods of fasting or illness, the body often switches to use its own proteins, and stored fats, to generate energy. Leucine, isoleucine, valine and threonine are essential amino acids meaning that the body cannot make them. Therefore, these amino acids come from ingested protein or from the breakdown of previously ingested and stored proteins.
Propionic acidaemia has several other names. These include ‘propionic aciduria’ since high levels of propionic acid are also seen in the urine (-uria = in the urine); ‘propionyl-CoA carboxylase deficiency’ after the characteristic enzyme abnormality or ‘ketotic hyperglycinaemia’ describing the presence of keto acids and glycine in the blood (hyper = high; -aemia = in the blood). The disease shows many similarities to methylmalonic acidaemia.
Overall, propionic acidaemia occurs in approximately 1 in 100,000 individuals globally. It is more common in the Arab population of Saudi Arabia (1 in 2000-5000) and the Inuits of Greenland (1 in 1000). The disease may also be more prevalent in Amish and Mennonite communities in the USA.
In propionic acidaemia, a mutation in one of two genes causes a deficiency in an enzyme called propionyl-CoA carboxylase. This enzyme is needed for the correct processing of isoleucine, valine, threonine and methionine amino acids and certain fats and cholesterol. When the enzyme is missing or shows reduced activity, these substances remain incompletely metabolised. This results in the production of propionic acid and other toxic substances. Keto acids are also generated, which are metabolic by-products created when the body resorts to using its own protein and fat stores for energy.
Propionic acidaemia is a recessively inherited genetic disorder, meaning that a child would only have the condition if both parents ‘carry’ the genetic mutation. Genes are arranged in structures called chromosomes that contain two strings or ‘alleles’. Offspring inherit one allele from their father and one from their mother. Carrying one copy of the mutated gene does not affect health, but when two mutated copies come together, the linked enzyme is deficient either in quantity or effect and the disease is expressed. For each and every pregnancy, there is a 1 in 4 chance of two carriers of the genetic mutation having a child with the disease.
Commonly, symptoms of propionic acidaemia develop in the first months of life. Infants fail to thrive due to feeding problems and vomiting. Their muscle tone is abnormally weak and they may show signs of extreme tiredness. Pronounced accumulation of metabolic by-products causes the blood and tissues become abnormally acidic (a condition known as metabolic acidosis). Keto acids also build up in the blood and tissues (known as ketoacidosis) and high levels are also seen in the urine. Blood levels of ammonia, a waste product of protein breakdown, and the amino acid glycine rise significantly. This early-onset form of the disease is often associated with rapid decline, culminating in severe dehydration, shock, heart abnormalities, brain damage, stroke, seizure and coma. Untreated, few infants survive such events.
Alternatively, propionic acidaemia may not manifest until later in childhood. In this case, individuals suffer intermittent metabolic ‘crises’, characterised by metabolic acidosis, ketoacidosis, extreme tiredness, vomiting, seizures and low muscle tone. The crises are triggered by infections, fever and periods without food, and are due to the body breaking down stored proteins and fats and releasing the toxic substances into the blood. Although children can be relatively healthy between attacks, for the majority there are long-term consequences. These include intellectual and learning disability, delayed development, abnormal movements due to a stroke, rigid muscle tone, poor growth/short height, seizures, osteoporosis, inflammation of the pancreas and an increased susceptibility to infection.
Blood and urine tests are the primary methods of diagnosis, evaluating levels of propionic acid, keto acids, ammonia and glycine. Enzyme analysis can be used to identify abnormal levels of propionyl-CoA carboxylase activity. Genetic tests are sometimes carried out to confirm a mutation in the genes linked to the disease. In certain countries, newborn screening programmes help detect the condition early.
Treatment of propionic acidaemia involves dietary restriction of protein generally and of methionine, threonine, valine and isoleucine specifically. The diet needs to be continued indefinitely and must be initiated only after consultation with a dietician. As with any restrictive diet, it is important to ensure optimal nutrition. While natural protein intake is limited, a formula free of methionine, threonine, valine and isoleucine is prescribed. A range of such formulas is available, designed specifically to meet the nutritional needs of children at different ages. These specially formulated powders contain a balanced mix of essential and non-essential amino acids, vitamins, minerals and carbohydrates to avoid malnutrition of other amino acids and to sustain normal growth and development in children. Several low-protein food products are also available.
During periods of illness, fasting and infection, aggressive treatment is initiated to prevent the body breaking down its own energy stores. This includes limiting protein intake, giving glucose and additional fluids, increasing carnitine supplementation plus, in some cases, using dialysis to reduce ammonia levels and correct metabolic acidosis.
Supplementation with carnitine, an enzyme involved in fatty acid metabolism, helps to neutralise the toxic metabolic by-products. Antibiotics may help reduce the production of propionic acid by the intestine and help reduce the frequency of infections. Biotin (vitamin B7) supplements may also prove useful in some individuals. Biotin is a co-factor that helps the enzyme propionyl-CoA carboxylase function.
Sufferers are advised to avoid long periods of fasting, especially during periods of illness. For example, eating a snack at bedtime reduces the duration of overnight fasting.
Early and appropriate intervention helps to reduce the risk of complications in propionic acidaemia. However, even with treatment individuals can develop permanent learning difficulties and movement disorders. Also, sufferers are often prone to infections, which require careful management to avoid triggering metabolic crises.
Eosinophilic Gastro-Intestinal disorders are a complex and chronic group of disorders. Put simply, Eosinophilic disorders occur when eosinophils (a type of white blood cell) are found in above normal amounts in various parts of the Gastro-Intestinal tract. When the body needs to attack an allegen, eg: a allergy triggering food or an airborne allergen, eosinophils respond by moving into the area and releasing toxins.
If the body produces too many of the eosinophils, they can cause chronic inflammation in the affected area. This can lead to damage to varying levels of the tissue in the affected area. All Eosinophilic disorders are chronic waxing and waning diseases. This means that the symptoms and severity can vary on a daily basis.
For more information, visit Families Affected By Eosinophilic Disorders (FABED) www.fabed.co.uk
Galactosaemia is condition in which the body cannot process or ‘metabolise’ the sugar galactose. The main dietary source of galactose is lactose, the natural sugar in milk and other dairy products. After milk is ingested an enzyme breaks the lactose down into glucose and galactose. Different enzymes then process the galactose into more glucose to be used by our bodies as energy. In people with galactosaemia, galactose is not metabolised and stays in the blood (hence the name galactos-: galactose; -aemia: in the blood). The levels build up and cause complications such as an enlarged liver, cataracts, brain damage and kidney failure. Untreated, galactosaemia can be life threatening.
The condition is rare, affecting only 1 in 70,000 people in the UK and 1 in 47,000 Caucasians in America. In Ireland, the condition is slightly more common, affecting 1 in 30,000 people overall, although it may affect as many as 1 in 480 people within traveller communities. People of African or Asian descent are less prone to the disorder than Caucasians. Males are affected as frequently as females and the condition manifests during the very first weeks of life.
Galactosaemia is a recessive genetic disorder. It results from an inherited mutation in the gene that makes an enzyme required for galactose metabolism. Mutations limit the ability of genes to generate the products they code for. In most people with galactosaemia, the deficiency is in the GALT enzyme (galactose-1-phosphate uridyltransferase). Less commonly, the enzymes galactokinase or UDP galactose epimerase may be involved.
Genes are arranged in structures called chromosomes that contain two strings or ‘alleles’. Offspring inherit one allele from their father and one from their mother. If a child receives two alleles with the galactosaemia mutation (i.e. one from each parent) they will develop the disorder. Parents will not be aware that they carry a galactosaemia mutation until giving birth to an affected infant. The disease does not manifest itself if the other allele in the chromosome is unmutated. In genetic terms, such parents are known as ‘carriers’ as they harbour and can pass on the genetic error but do not have the disease itself.
For each and every pregnancy, there is a 1 in 4 chance of two carriers having a child with galactosaemia.
Normally, no abnormalities are obvious at birth. However, symptoms and signs of galactosaemia appear in infants once they are introduced to milk – either breast milk or formula – due to the rapid accumulation of galactose.
The features vary in severity. Early indicators in infants are feeding difficulties, vomiting, failure to gain weight, tiredness, irritability and convulsions.
Examination and tests may reveal the infant to have amino acids in the urine, collections of fluid in the abdomen, clouding of the lens of the eyes (cataracts) or a full fontanelle (the soft area on the baby’s skull). Babies may also develop jaundice, have enlarged livers and show signs of liver damage. Sufferers are prone to E. coli sepsis – a serious inflammation of the whole body due to a bacterial infection.
Additionally, children with galactosaemia show a characteristic delayed development in speech, language and learning. Specifically, there can be problems with organised speech (oromotor dyspraxia) and possibly with movement (motor dyspraxia) making children slow in finishing tasks. Difficulties with maths and reading are also common. The reason for these developmental complications is not known. They can affect many aspects of a child’s life including social and family life, school, work and daily activities.
Females are affected by a number of gynaecological complications of galactosaemia. The majority of adolescent women with galactosaemia do not go into puberty at the right time. Or their periods may stop unexpectedly. This is due to a condition called hypergonadotrophic hypogonadism, which is linked to poor functioning of the ovaries. Women with galactosaemia may also experience premature ovarian failure, which causes infertility. Although some women with galactosaemia are successful in becoming mothers, reduced fertility is a problem for the majority.
Finally, adults with galactosaemia are usually short in height and may suffer coordination problems (ataxia) and tremor.
Galactosaemia is detected in the first few weeks of life since symptoms begin once the infant starts to ingest milk. The greatest indicators of the condition are failure to thrive and E. coli sepsis.
Diagnosis is confirmed by measuring the activity of the galactose-metabolising enzymes in the blood. Tests can also be carried to out to detect galactose or related compounds in the urine.
In the USA and in certain European countries, newborn infants are screened for galactosaemia using a heel-prick test. In the UK, screening is only carried out in Scotland.
Galactosaemia is a lifelong condition, for which there is no cure. However, it can be managed successfully by excluding galactose from the diet. This must be started immediately after diagnosis and only under the advice of a nutritionist. The diet must be followed throughout life.
Galactose-restriction primarily involves avoiding milk and other dairy products including cream, yoghurt, cheese, butter and milk powder due to their lactose content. Certain fruits and vegetables (such as figs and certain peas and beans) contain galactose so total elimination is difficult. A galactose-restricted diet rapidly improves liver problems and infants begin to gain weight. Cataracts also improve over time, and usually resolve completely.
Many prepared foods contain milk or milk products. Some of these may not be so obvious – for example, whey, casein, calcium caseinate and lactalbumin all indicate milk or lactose content, and some food flavourings and colouring such as caramel may contain milk. Food labelling has improved over recent years in the UK in an effort to clarify which products contain milk. Dieticians can provide invaluable guidance on understanding food labelling and lists of milk-free products are available from most supermarkets. Nutritionally complete infant formulas are available for the sole source of nutrition for babies with galactosaemia or as a supplementary feed for older children. Dairy-free and milk-replacement foods and ingredients are available for older children and adults.
Certain complications continue, however, despite dietary galactose reduction. Specialised intervention may be required for speech, language and learning problems. Premature ovarian failure, plus a dairy-free diet, increases the risk of osteoporosis in later life. Calcium supplements, hormone-replacement therapy and regular weight-bearing exercise can help to maximise bone mineral density. Osteoporosis can affect both sexes but is a particular concern for females. Oestrogen therapy may be indicated to trigger puberty in those with hypergonadotrophic hypogonadism. Long-term oestrogen-replacement therapy can help stabilise menstrual cycles. For women requiring fertility treatment, approaches using donated eggs may be an option.
The complications of galactosaemia are not life threatening. Children and adults living with galactosaemia and following a galactose-restricted diet can look forward to an otherwise healthy and active life.
Epilepsy is the most common neurological disorders and can be defined as the condition of unprovoked, recurring seizures. It is thought that up to 5% of the worlds population may have some form of seizure in their life time. Only those with the recurring seizures will be diagnosed with Epilepsy. It can occur in male or female, adult or child.
The World Health Organization (WHO) estimate the prevalence to be approximately 8.2 per 1000 of the population. This equates to 50 million people across the world. It also means that there are approximately 100 million people who have either suffered from epilepsy, are suffering from epilepsy or will suffer from epilepsy.
Individuals with epilepsy may experience subtle interruptions of awareness and responsiveness to a major convulsion attack of the whole body. It cannot be considered as a single medical condition. There are many reasons why an individual would have these attacks, also known as seizures or fits.
Studies have shown that 70% of individuals diagnosed with Epilepsy can be treated successfully with anti epileptic drugs. According to the WHO:
Epilepsy is a chronic disorder characterized by recurrent seizures, which may vary from a brief lapse of attention or muscle jerks, to severe and prolonged convulsions. The seizures are caused by sudden, usually brief, excessive electrical discharges in a group of brain cells (neurones). In most cases, epilepsy can be successfully treated with anti-epileptic drugs.
They fail to mention the Ketogenic Therapy (or Ketogenic Diet as it is also known). The ketogenic diet should be tried more frequently then it is at the moment. If anti-epileptic drugs have had no impact in on 2 occasions then the Ketogenic Diet should be tried.
This site promotes the Ketogenic Diet and provides support to Health Care Professionals, Parents, Patients and Carers.
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Food allergies are reproducible reactions which are caused by the body’s immune system responding to a protein in a particular food. In the case of cows milk allergy (or cows milk protein allergy), the immune system reacts to the milk protein and this triggers an allergic reaction. The reaction can present itself in different ways so it can be difficult to diagnose immediately.
Allergies are different to intolerances; allergies must always involve an immune reaction to a protein whereas an intolerance is a reaction to any food or food product and tend to be more common than allergies. Food intolerances are typically dose-dependant therefore the more of the food component that you are exposed to the worse the symptoms.
Food aversion is different to both allergy and intolerances. With food aversion there is no organic disease present, but a strong dislike to a food leads to the complete avoidance of it. Food aversions are psychological rather than causing clinical symptoms. Simply, allergy is defined as adverse health affects derived from an immune response, or, immunity gone wrong.
Allergy can be quite complex, and no single cause has been identified. The causes of food protein allergies have been attributed to a combination of factors. These causative factors include genetic predisposition, individual immune status, exposure and environmental factors.
Various immunological diseases have been found to be more common in industrialised countries than in the developing world. Studies in third world countries have found that there is an increase in immunological disorders as the country develops and grows ‘cleaner’ The use of antibiotics and antibacterial cleaning agents has also been associated with asthma and other allergic diseases.
Research does suggest the more hygienic we become the less exposure we have in early childhood to common allergens and therefore the more likely we are to develop allergy related symptoms.
Cows milk allergy is the most common food allergy in infants, it currently affects about 2-3% of infants but this has been found to be increasing, some research has suggested that up to 7% of infants may be affected by cows milk allergy. At the age of one year the allergy will still remain in about 45% of patients.
The majority of children will grow out of the allergy by the ages of 3-5 years, however a minority of patients may still have cows milk allergy throughout childhood.
Allergy typically leads to symptoms in one or more of the following three systems:
Cows milk allergy can result in a number of symptoms including skin rash/severe eczema, runny nose/eyes, constipation, diarrhoea, colic, acid reflux, wheezing, constant crying and general distress. The symptoms can either occur one at a time or in a combination. It is rare that all or even a few of these symptoms will be present at once; generally one will appear at a time. One of these symptoms on their own may not necessarily indicate cows milk allergy. It may only be after a significant period of time, when a number of symptoms have been displayed that cows milk allergy may be suspected. Because of the nature of the symptoms it can be difficult to diagnose cows milk protein allergy immediately.
Depending on what type of immune reaction occurs will depend on whether symptoms appear immediately or if they are late/delayed symptoms. The time between exposure to the allergic protein and the display of symptoms will provide an indication of the type of immune reaction that is occurring. Allergic reactions can be either IgE mediated or non-IgE mediated.
In cows milk protein allergy, when the cows milk protein is consumed, the immune system responds to the cows milk protein by releasing antibodies. In cows milk allergy these are called IgE antibodies and they are specific to cows milk protein. These IgE antibodies then bind with mast cells, these are now sensitised. When cows milk protein is recognised in the body for a second time, the cows milk protein binds to the mast cells and an immediated response or reaction occurs.
IgE mediated allergy therefore displays symptoms relatively quickly, and only a small dose is needed for the reaction to occur.
Non-IgE mediated allergy is slightly different. When cows milk protein is first ingested the immune system produces cells called T-cells. These T-cells however are unable to recognise the cows milk protein straightaway, the cows milk protein has to go through certain processing before it can be recognised. This processing can take anywhere up to 24-46 hours. Therefore non-IgE mediated allergy does not display symptoms immediately; instead symptoms have a delayed onset. Non-IgE allergy can also respond to smaller protein fragments than IgE, as well as whole proteins.
Cows milk allergy is often non-IgE mediated or a combination of IgE and non-IgE. Due to this, not all patients will be able to tolerate hydrolysed formulas in these cases amino acid based formulas may be favoured.
If cows milk allergy is suspected, obtaining a detailed medical history is important. It needs to be determined whether or not it is food related. The first onset of symptoms needs to be identified, timing of symptoms and types of symptoms should be identified in order to determine if it is rapid or delayed onset allergy and how severe the allergy is as this may influence the treatment chosen.
Accuracy of diagnosis is essential, if a problem food is left in the diet the symptoms will persist. If foods are removed from the diet unnecessarily, the there may be a risk of nutritional deficiency.
Once doctors have detailed information, they can decide which diagnostic tests may be required. If the symptoms are appearing quite quickly then IgE mediated allergy may be suspected (IgE simply relates to the type of immune response that is triggered), if the symptoms seem to be delayed in appearing then non-IgE mediated allergy may be suspected.
If IgE mediated allergy is suspected then a skin prick test can be carried out.
This test is usually carried out on the forearm or if necessary on the back. A drop of the allergic protein is placed on the skin and the skin is pricked through the trop. If a reaction occurs then the area can become red and swollen almost immediately. This should only by carried out by a doctor or specially trained health care professionals.
The advantage of such a test is that it is quick, inexpensive and the results can be seen quickly. It has been suggested that skin prick testing with food allergens is less reliable than with dust or pollens. It has been suggested now that skin prick testing is only effective in identifying about 50% of IgE mediated allergy.
This is a blood test which can give an indication of which allergens a person is allergic to. A blood sample is taken and the amount IgE antibody specific to a particular antigen is measured. If the levels of the specific IgE antibody are high then this would indicate that the person is allergic to the particular antigen it was for. For example if a person displayed high IgE antibodies specific for cows milk protein it would suggest that person had cows milk allergy.
If test are negative then it does not necessarily mean they do not have an allergy, just that the allergy they may have is not IgE mediated.
For confirmation of cows milk allergy then milk should be excluded from the diet, once symptoms have cleared then the patient may be challenged with cows milk under medical supervision.
The dietary treatment of cows milk protein allergy requires a strict milk protein free diet. Which poses a problem in some infants as standard infant formulas are based on casein or whey protein from cows milk. This can have implications in infants where milk is the only component of the diet up until 6 months of age i.e. sole source of nutrition during this time, and remains a major component of the diet throughout early childhood.
In order to prevent any nutritional deficiencies during infancy a suitable alternative needs offered to ensure that nutrient requirements are met.
This is important as a whole food group is now off limits, the nutrients and energy which infants would normally get from standard infant formulas needs to be replaced. Readily available alternatives such as soya or goat milk are unsuitable in infants. If an infant has cows milk allergy they may have allergy to other animal milk proteins therefore these cannot be used as an alternative.
The formulas developed specifically for cows milk protein allergy are medical foods. Foods for special medical purposes are subject to clinical trials to provide evidence of their effectiveness before they are able to be used in patients. Special medical formulas that are most effective will be hypoallergenic formulas. This means that the formulas will have been subject to clinical trials to prove their effectiveness and safety in severe cows milk allergy patients.
Crohn’s disease is a chronic inflammatory bowel disease. Inflammatory bowel disease (IBD) is a collective term used to describe illnesses that cause inflammation of the gastrointestinal tract. Ulcerative colitis and Crohn’s disease are the two most common of these illnesses. Unlike Ulcerative colitis, where the site of ulcer or inflammation is usually in the large bowel, Crohn’s disease can cause inflammation in one or more parts of the gastrointestinal tract lining, anywhere from mouth to anus. Crohn’s disease is typically characterised by affected segments of the gut being separated by apparently normal areas. The inflammation can cause scarring which can result in the walls of the bowel to thicken; this thickening of the walls is called a stricture. Crohn’s disease results in periods of remission and relapse.
Crohn’s disease can affect any age group, usually from age eight years and onwards, however, childhood cases are increasing and sometimes they can be as young as five. It is rarely diagnosed in very early childhood. It can affect any race and gender. The prevalence of Crohn’s disease is estimated to be around 50 to100 per 100,000 people, therefore affects about 60,000 people in the UK. It can affect people at any age but the incidence is higher in 15 to 30 year olds. Approximately 25% of newly diagnosed cases of Crohn’s disease are in paediatric patients.
Crohn’s disease is a chronic disease; therefore can cause a variety of symptoms which can be slow starting and long lasting. Symptoms may include abdominal pain, urgent diarrhoea (sometimes with blood and/or mucous) and rectal bleeding. Poor appetite caused by a combination of inflammation and pain, this leads to poor growth in children and often significant weight loss. Symptoms may affect some people worse than others and is not uncommon to feel generally tired and lethargic.
There is no definitive answer to this, many theories have been put forward, and possible suggested causes include, genetic factors, diet, smoking, infectious agents, role of antigens and abnormal immune responses have also so been proposed as possible contributors to the disease.
Inflammation of the liver can occur although this is rare in paediatric patients. Mouth ulcers, thickening of the lips, skin rashes and sore eyes may also features. These symptoms are generally easily treated but it is important to inform your health care professional of any unusual physical changes you may notice.
Crohn’s disease is a chronic illness, so it cannot be completely eliminated. However, there are steps which can be taken to manage the disease, therefore minimise its effects and prevent a relapse. Crohn’s disease symptoms and severity can vary in different patients therefore patient treatment may also differ. Health care professionals will prescribe the most suitable form of treatment for an individual in order to meet their specific needs. Once treatment has started symptoms will begin to improve and the aim then will be to maintain remission so you can continue with day to day life without disruption.
If Crohn’s disease is suspected a combination of investigations will be carried out to confirm the diagnosis. Blood tests are particularly useful as they can measure a number of different factors in order to monitor your condition There are several tests that can be carried out in order for the doctor to make an accurate diagnosis and start you on the most suitable treatment.
The aim of treatment in Crohn’s disease is to induce remission by relieving symptoms and resolving inflammation, promoting optimal growth particularly in paediatric patients and to correct any nutritional deficiencies that may have developed. Treatment can be either dietary, drugs, surgery or a combination of these. Dietary (Nutrition therapy) is often used as a first line treatment in the management of Crohn’s disease especially paediatric Crohn’s, sometimes in conjunction with drugs. Surgery, although an option, is used as a last resort in patients which have been unresponsive to dietary and/or drug treatments. Both drugs and dietary treatments have their benefits. Drugs are easy to use and convenient; therefore aid good patient compliance and good remission rates can be achieved. However, drug resistance can be demonstrated by some patients and drugs or combinations of drugs can result in many unwanted side effects. Dietary therapy is an option for patients with Crohn’s disease, particularly paediatric patients where there are concerns regarding growth. Dietary therapy has advantages, as it can relieve symptoms without the side effects associated with drug treatments. Dietary therapy also provides essential nutritional support and can aid recovery by correcting any nutritional deficiencies that may have developed.
There are a number of different drugs types which can be used in the treatment of Crohn’s disease, they include:
Surgery is only opted for if drug and/or dietary therapies have proven unsuccessful. If the affected area of the gut is localised enough then surgery can be performed to remove the affected part of the gut and rejoin the two healthy parts. This however does not cure Crohn’s as it is still possible for it to reappear in previously unaffected areas. Surgical procedures may also be used to reduce narrowing that can result from inflammation of the gut wall.
Dietary therapy is increasingly being used as a first line treatment of Crohn’s disease particularly in paediatric patients. Dietary therapy has been found to be as effective as steroids with minimal if not any side effects. It also has the benefit of improving the nutritional status of the patient and promotes growth in children. The principle of dietary therapy is to administer a liquid diet for a set period of time, this can vary anywhere between 2 to 6 weeks sometimes longer in paediatric patients. The exclusive liquid diet aims to induce remission in the patient and maintain it.
Phenylketonuria (or PKU as it is commonly called) is an inherited (autosomal) disorder of phenylalanine metabolism, caused by a deficiency of the enzyme phenylalanine hydroxylase. It is the most common Hyperphenylalaninemia and can be classified into 3 groups:
People with this condition will lead normal lives as long as they follow their prescribed treatments.
This condition is the result of the body being unable to breakdown Amino Acids. These amino acids come from protein which is found in the food we eat. They are considered as the building blocks for our bodies. An individual with PKU does not have enough of the enzyme phenylalanine hydroxylase (PAH) to breakdown the phenylalanine amino acid into tyrosine (another amino acid).
A person with PKU will have inherited two non-working PKU genes. One will be inherited from the mother and the other from father. These parents may already have PKU themselves others who are carriers may not discover it until they have a baby with PKU. A "carrier" is a person who has one non-working gene and one working gene. They are healthy, but can pass the non-working gene on to their child.
Classical PKU affects between 1 in 10,000 and 1 in 20,000 depending on the country of origin. This can be considerably higher in the Eastern Mediterranean region (1 in 4,000 in Turkey and 1 in 3,627 in the Islamic Republic of Iran), however it has been reported that Ireland, Poland and the Czech Republic also have high incidence rates.
The higher rates of incidence can be primarily attributed to the high degree of consanguineous marriages in those regions.
Most countries identify infants with PKU through their national newborn screening programmes. Where there is no programme in place, symptoms are likely to develop a few months after birth and include:
If left untreated, the child is likely to experience behavior problems and developmental delays. There may be severe brain problems occur, such as mental retardation and seizures.
As mentioned already, most of the developed world has newborn screening programmes for PKU. This involves taking a small sample of blood from the child’s heel (the Guthrie test) sometime between the 3rd and 14th day of its (this very much depends on the local protocol). The baby must have had milk feeds or parenteral nutrition for at least 48hours before the test is carried. If the screening test is abnormal, other tests will be needed confirm or exclude if the child has PKU.
Other Tests:
Treatment for phenylketonuria involves eating a controlled diet that is low in protein. Therefore, someone with PKU must avoid eating foods that are high in protein, such as meat, poultry, and dairy products. To review examples of the required recipes click here. To watch videos of the recipes being prepared click here.
A phenylalanine free protein substitute, with added tyrosine is recommended in order to lower the amount of phenylalanine that accumulates in the child's body. This form of treatment usually works well and allows the child to grow and develop normally. A list of products from SHS can be found here.
Research has shown that this diet should be followed for life. Keeping blood phe levels in the safe range helps to prevent problems with concentration and IQ development. Unfortunately some countries still do not advocate the diet for life protocol. It is never too late to go back "on diet." Even previously untreated patients who have development issues will benefit.
Watch an interview of a carer talking about how her patient has benefited from going back on diet;
Women with have PKU who are hoping for a family of their own must carefully control their phenylalanine levels. Babies born to mothers who have high phenylalanine levels during pregnancy are at risk for mental retardation, physical growth problems, and congenital heart disease.
There are several types of Tyrosinaemia caused by disorders of tyrosine metabolism, which are relatively rare.
Tyrosinaemia type I is caused by a deficiency of fumarylacetoacetate hydroxylase resulting in severe liver and kidney failure and eventually death. The aim of dietary management is to prevent the accumulation of phenylalanine, tyrosine and sometimes methionine by means of a low protein diet. The protein requirements are met by supplementing the diet with a tyrosine, phenylalanine and/or methionine free amino acid mixture. If NTBC is prescribed then a phenylalanine and tyrosine free protein substitute is normally used. A phenylalanine, tyrosine and methionine free protein substitute is used only when the patient is unresponsive to NTBC or it is unavailable. Whilst dietary management is important in Tyrosinaemia, NTBC has significantly improved management and survival in Tyrosinaemia type I.
Tyrosinaemia type II is caused by a deficiency of tyrosine aminotransferase leading to eye lesions, skin lesions and neurological complications. The aim of dietary management is to prevent the accumulation of phenylalanine and tyrosine by means of a low protein diet. The protein requirements are met by supplementing the diet with a tyrosine and phenylalanine free amino acid mixture.
Tyrosinaemia type III is a very rare form of tyrosinaemia resulting in convulsions, ataxia and mental retardation. The aim of dietary management is to prevent the accumulation of phenylalanine and tyrosine by means of a low protein diet. The protein requirements are met by supplementing the diet with a tyrosine and phenylalanine free amino acid mixture. Guidance on amino acid intakes have been extrapolated from MRC guidelines on PKU management.
Report of Medical Research Council on the Dietary Management of Phenylketonuria. Recommendations on the Dietary Management of Phenylketonuria. Arch. Dis. Child. 1993: 68; 426-7.
Dixon M., MacDonald A, White F. Disorders of Amino Acid Metabolism, Organic Acidaemias and Urea Cycle Defects Phenylketonuria in Lawson M, Shaw V (eds.). Clinical Paediatric Dietetics. Oxford:Blackwell Science, 2001,p233-294.
Holme E, Linstedt S. Tyrosinaemia type I adn NTBC (2-(2-nitro-4-triflourom othylbenoyl)-1,3-cyclohexanedione). J. Inherit. Metab. Dis. 1998:21;507-517.
Ellaway CJ., Holme E, Standing S. et al. Outcome of Tyrosinaemia type III. J. Inherit. Metab. Dis 2001:24;824-32.
Maple syrup urine disease is a genetic disease characterised by incomplete metabolism of the amino acids leucine, isoleucine and valine. It owes its unusual name to the characteristic sweet-smelling urine of those affected.
In individuals with this disease, poor processing of leucine, isoleucine and valine causes a build up of these molecules and their by-products in the blood and urine. Untreated, this can cause seizures, severe brain damage and coma. Few infants survive without intervention. The condition shows similarities to isovaleric acidaemia, in which leucine metabolism is affected.
Amino acids are the building blocks of proteins. After eating proteins, the body ‘metabolises’ or breaks them down into amino acids. Animal proteins include dairy products, meat, eggs and fish. Proteins are also found in plants including soy, legumes, grains and nuts. The body uses the amino acids to make its own proteins essential for life – for example enzymes; structural proteins in muscles, hair, skin, cells and cartilage; proteins that generate movement in muscles; or those involved in cell functioning or immune responses. In periods of fasting or illness, the body often switches to use its own proteins to generate energy.
Leucine, isoleucine and valine are essential amino acids meaning that the body cannot make them. Therefore, these amino acids come from ingested protein or from the breakdown of previously ingested and stored proteins. Leucine, isoleucine and valine are classified as ‘branched amino acids’, which describes their specific chemical composition.
Another name for maple syrup urine disease is branched-chain ketoaciduria. This describes the presence in the urine of keto acids. These are metabolic by-products created when the body resorts to using its own protein and fat stores for energy.
Globally, around 1 in 185,000 people live with maple syrup urine disease. It may be more common in Amish or Mennonite communities in the USA, affecting as many as 1 in 380 newborns.
The disease may be linked to a mutation in any of four genes. These genes code for proteins that work together as a complex called the branched-chain alpha-keto acid dehydrogenase complex. The subunits of the enzyme complex are termed E1α, E1β, E2, and E3. When functional, the complex is involved in the metabolism of leucine, isoleucine and valine. Genetic mutation reduces or eliminates the function of complex, thus interfering with the correct processing of these amino acids. In general, the severity of the disease is linked to the degree of enzyme activity that remains.
Maple syrup urine disease is a recessively inherited genetic disorder, meaning that a child would only have the condition if both parents ‘carry’ the genetic mutation. Genes are arranged in structures called chromosomes that contain two strings or ‘alleles’. Offspring inherit one allele from their father and one from their mother. Carrying one copy of the mutated gene does not affect health, but when two mutated copies come together, the linked enzyme is deficient either in quantity or effect and the disease is expressed. For each and every pregnancy, there is a 1 in 4 chance of two carriers of the genetic mutation having a child with maple syrup urine disease.
There are five types of maple syrup urine disease: classic, intermittent, intermediate, thiamine-responsive and dihydrolipoyl dehydrogenase deficient forms.
The classic form is the most common and severe, and is associated with the lowest level of remaining enzyme activity. Infants appear healthy at birth then symptoms develop from about the age of 1 to 2 weeks. These include poor feeding, vomiting, dehydration, weight loss and extreme tiredness. Pronounced accumulation of metabolic products causes the blood and tissues to become abnormally acidic (metabolic acidosis). Keto acids also build up in the blood, tissues and urine (ketoacidosis). The urine takes on the characteristic smell of maple syrup. Abnormal neurological signs such as floppiness, seizures and abnormal posturing of the arms may develop and neurological decline continues if treatment is not initiated.
The other types of maple syrup urine disease appear later in childhood and are less severe than the classic variant. Those with intermittent disease may have up to 20% remaining enzyme activity. The disease tends to reveal itself between the ages of 5 months and 2 years, although it can be as late as 5 years before symptoms develop. Metabolic crises (i.e. metabolic acidosis, ketoacidosis and high levels of the amino acids) occur intermittently. Otherwise, growth and development are quite normal. The crises are triggered by infections, fever and periods without food, and are due to the body breaking down stored proteins and releasing the toxic substances into the blood.
Individuals with intermediate-type maple syrup urine disease have up to 30% enzyme activity. They show gradual neurological problems due to slowly increasing levels of amino acids. If untreated, these problems affect the brain and affect intellectual functioning. This form is usually diagnosed before the age of 7 years.
Thiamine-response maple syrup urine disease is similar to the intermediate type except that, as the name suggests, individuals respond well to treatment with thiamine (vitamin B1). Enzyme activity is usually up to 40% of normal levels.
Finally, the E3-deficient variant is similar to intermediate maple syrup urine disease except an additional type of acidosis occurs, known as lactic acidosis. This form is extremely rare, manifests between the ages of 8 weeks and 6 months, and is characterised by progressive brain damage and movement disorder.
The distinctive smell of the urine usually raises the suspicion of maple syrup urine disease. Blood and urine tests showing high levels of the amino acids leucine, isoleucine and valine, and signs of ketacidosis and metabolic acidosis confirm the diagnosis.
In some countries, infants are routinely screened for maple syrup urine disease at birth.
Maple syrup urine disease is treated through dietary restriction of leucine, isoleucine and valine. The aim of treatment is to reduce levels of these amino acids in the body to prevent them causing brain damage. This diet needs to be continued indefinitely and must be initiated only after consultation with a dietician.
The leucine-, isoleucine- and valine-restricted diet must be managed carefully to ensure optimal nutrition. As such, natural protein intake is limited and a formula free of leucine, isoleucine and valine is given. A range of such formulas is available, designed specifically to meet the nutritional needs of children at different ages. These specially formulated powders contain a balanced mix of essential and non-essential amino acids, vitamins, minerals and carbohydrates to avoid malnutrition of other amino acids and to sustain normal growth in children. Several low-protein food products are also available.
During periods of illness, fasting and infection, aggressive treatment is initiated to prevent the body breaking down its own proteins. This comprises giving additional fluids, carbohydrates and fats plus, in some cases, dialysis to reduce amino acids levels in the blood.
Individuals with intermittent maple syrup urine disease may only require treatment during periods where there is increased risk of metabolic crisis.
A trial of thiamine supplementation lasting for at least 3 weeks is normally recommended for all individuals with maple syrup urine disease, to identify those with thiamine-response disease.
Although there is no cure, with diet and correct management of crises, most individuals with maple syrup urine disease are able to live normal lives.
Homocystinuria is a genetic disease in which incorrect metabolism of the amino acid methionine causes the amino acid homocysteine to accumulate in the blood and higher levels to be excreted in the urine.
Amino acids are the building blocks of proteins. After eating proteins, the body breaks them down into amino acids. Animal proteins include dairy products, meat, eggs and fish. Proteins are also found in plants including soy, legumes, grains and nuts. The body uses the amino acids to make its own proteins essential for life – for example enzymes; structural proteins in muscles, hair, skin, cells and cartilage; proteins that generate movement in muscles; or those involved in cell functioning or immune responses. In periods of starvation, amino acids can be redirected to generate energy for the body. Methionine is present in animal and plant proteins, especially sesame seeds, nuts, spinach, mushrooms, broccoli, potatoes, fish and meat. However, homocysteine is produced only by our bodies as part of the processing of methionine.
Raised homocysteine levels in the blood adversely affect multiple areas of the body including the eye, muscles, connective tissue, brain and blood vessels. The most serious complications are related to the damage to blood vessels. High levels of homocysteine in the blood promote atherosclerosis or ‘hardening’ of the arteries. Besides occurring in individuals with homocystinuria, atherosclerosis is more commonly seen in adults with a history of diabetes, smoking, high blood pressure and high blood levels of ‘bad’ cholesterol. In atherosclerosis, the walls of large and medium arteries become inflamed, less elastic and more likely to form fatty lumps or ‘plaques’. The plaques can block the blood vessels, reducing or preventing blood flow to the organ that the artery supplies. The consequences can be life-threatening. The exact event will depend on the site of the blockage. For example, a heart attack can occur if the obstruction stops blood flow to the heart. Blockage in the deep vein of the leg, pelvis or sometimes the arm can result in deep vein thrombosis (DVT). If the clot from a DVT breaks free, it can travel in the circulation and impede blood supply to the lungs causing pulmonary embolism. Finally, a stroke could occur if the brain is affected.
Worldwide, only 1 in 344,000 people have homocystinuria, making the condition extremely rare. However, some studies suggest the incidence may be higher in Ireland where up to 1 in 65,000 people could be affected.
Most commonly, the defective gene in homocystinuria is the one that codes for an enzyme known as cystathionine β-synthase. This enzyme is involved in processing methionine into smaller molecules via a pathway of reactions. When cystathionine β-synthase is deficient, the pathway stops after the production of homocysteine, which is why this molecule accumulates and causes problems.
Homocystinuria is recessive in nature, meaning that a child would only have the condition if both parents ‘carry’ the genetic mutation. Genes are arranged in structures called chromosomes that contain two strings or ‘alleles’. Offspring inherit one allele from their father and one from their mother. Carrying one copy of the mutated gene does not affect health, but when two mutated copies come together, the linked enzyme is deficient either in quantity or effect and the disease is expressed. For each and every pregnancy, there is a 1 in 4 chance of two carriers of the genetic mutation having a child with homocystinuria.
Newborn infants with homocystinuria rarely show any symptoms. Later in infancy, failure to thrive or mildly delayed development may be the only early clues that a problem exists.
As the child grows, other symptoms of homocystinuria begin to show. The pattern and severity of symptoms vary greatly between patients. Characteristic features include increasing visual problems, dislocation of the lens of the eye and glaucoma. Certain physical signs are also indicative, including flushing across the cheeks, chest deformities, curved spine, long limbs, ‘knock knees’, high arches on the feet, spidery fingers, and a tall, thin build. The joints may be tight and the bones less dense than normal due to osteoporosis. There may be evidence of plaque formation in the arteries, although in many cases this produces no symptoms at first. Finally, patients may have a low IQ, have intellectual development difficulties or psychiatric disorders.
Recognising homocystinuria is difficult in infants because many show no symptoms or, if present, early symptoms are vague and could have a number of causes. Visual problems, especially lens dislocation, are usually the main indicators, and a tall, thin build raises suspicion of the condition.
Diagnosis of homocystinuria is confirmed by an amino acid test of the blood and urine, which shows high levels of homocysteine and methionine. Other tests used for diagnosis and evaluation of the condition include genetic testing, liver biopsy and enzyme assays, x-rays, skin biopsies and eye examinations.
In certain countries, homocystinuria is identified through routine newborn screening programmes.
Treatment aims to normalise homocysteine levels. In infants the goal is to reduce the risk of all complications whereas in older individuals the priority is to prevent atherosclerosis-related complications.
Approximately 50% of patients respond to high doses of vitamin B6, also known as pyridoxine. This vitamin is a ‘co-factor’ in methionine metabolism, which means that it is involved in the natural processing of methionine. Supplementation must continue over the long term in those who respond to treatment. Responders to vitamin B6 supplements are also advised to limit their dietary intake of protein.
Non-responders to vitamin B6 are treated with a low-methionine diet. Started early, the diet can reduce the risk of complications and the impact of intellectual disability. It must continue for the individual’s lifetime, and should only begin after consultation with a dietician. Methionine restriction is achieved by limiting the intake of natural proteins in the diet. To prevent malnutrition of other amino acids, a methionine-free amino acid formula is taken. There is a range of general methionine-free powders formulated to meet the nutritional needs of individuals of various ages. These contain a balanced mix of essential and non-essential amino acids, vitamins and minerals, with minimal carbohydrates. Special low-protein food products are also available.
Most individuals with homocystinuria also require treatment with a drug called trimethylglycine, or betaine. This converts homocysteine to methionine, thus reducing levels of homocysteine in the body. However, this treatment is not suitable for infants.
For some people, supplementation with folic acid and/or vitamin B12 is useful. Like vitamin B6, these are co-factors in methionine metabolism so help correct the abnormal processing. Adding the amino acid cysteine to the diet can also be useful.
Individuals with homocystinuria may also require therapy for the complications of this disease, for example lens replacement surgery and osteoporosis treatment.
Although no cure exists for homocystinuria, long-term treatment to reduce homocysteine levels significantly reduces the risk of life-threatening vascular events. A benefit is seen even if homocysteine levels do not return fully to normal levels.
Urea cycle disorders are a group of inherited diseases characterised by incomplete ‘metabolism’ or processing of nitrogen. This metabolic fault causes ammonia to build up in the blood, which poisons the brain.
After we eat protein, our bodies break them down into amino acids. As part of this processing, nitrogen is generated as a waste product. A multi-step pathway of reactions known as the urea cycle is responsible for removing this nitrogen from the blood, turning it into urea and excreting it via the kidneys in urine. The steps of the pathway require enzymes and/or ‘co-factors’ (enzyme helpers) that perform a specific task in the overall processing of nitrogen to urea. In individuals with urea cycle disorders, one of the enzymes or an enzyme ‘co-factor’ from the pathway is absent or has reduced activity. The consequence of the deficiency is that the urea cycle produces ammonia instead of urea.
There are six different types of urea cycle disorders. Each is named after the deficient urea cycle enzyme or, in the case of NAGS, a deficient co-factor:
Animal proteins are found in dairy products, meat, eggs and fish. Proteins are also found in plants including soy, legumes, grains and nuts. The body uses the amino acids from proteins to make its own proteins essential for life – for example enzymes; structural proteins in muscles, hair, skin, cells and cartilage; proteins that generate movement in muscles; or those involved in cell functioning or immune responses. Requirements are higher in childhood as proteins are needed to support growth and development. Certain amino acids must come from the diet, as the body cannot manufacture them itself. These are known as ‘essential’ amino acids. In periods of fasting or illness, the body often switches to use its own proteins, and stored fats, to generate energy.
Overall, urea cycle disorders are thought to occur in at least 1 in 30,000 individuals globally, although this may be an underestimation of the true prevalence. OTC is the most common condition, affecting 1 in 30,000 people. CPS and ASL are seen in 1 in 60,000 and 1 in 70,000 individuals respectively. The remaining conditions, NAGS, ASS and ARG, are much more rare.
In CPSI, OTC, ASS and ASL, the condition is due to a defect in the gene that codes for an enzyme of the urea cycle. The enzyme has reduced activity or is missing completely as a result. A genetic defect is also responsible for NAGS, although the gene codes for an enzyme co-factor.
NAGS, CPS, ASS, ASL and ARG are recessively inherited genetic disorders, meaning that a child would only have the condition if both parents ‘carry’ the genetic mutation. Genes are arranged in structures called chromosomes that contain two strings or ‘alleles’. Offspring inherit one allele from their father and one from their mother. Carrying one copy of the mutated recessive gene does not affect health, but when two mutated copies come together, the linked enzyme is deficient either in quantity or effect and the disease is expressed. For each and every pregnancy, there is a 1 in 4 chance of two carriers of the genetic mutation having a child with the disease.
OTC, however, is X-linked, so it is mainly male infants who are affected. In X-linked diseases, the condition is only passed to infants if the mother is a carrier with a defective X chromosome. Women have two X chromosomes so the normal X chromosome will mask a defect on the other X chromosome to a certain degree. Therefore, female offspring of a carrier mother will either be carriers of the disease and show no symptoms or will have a mild version of the disease. In males, there is one X chromosome and one Y chromosome so any defect on the X chromosome will be expressed and they will show the full features of the disease.
The severity of urea cycle disorders varies according to how early the symptoms appear, the degree of residual enzyme activity and the position of the affected enzyme or co-factor within the urea cycle.
OTC in boys and CPS present very early, perhaps in the first few days of life, as do cases of ASS, ASL and NAGS with complete loss of enzyme or co-factor activity. Individuals with such early-onset variants typically have severe disease features and a poor prognosis. They seem healthy at birth but protein intake triggers symptoms due severe accumulation of ammonia in the blood. Early signs are vomiting, problems with feeding and extreme tiredness. Progressive brain damage manifests as poor muscle tone, seizures and abnormally fast breathing (hyperventilation). The liver may also become enlarged. Untreated, there is a high risk for these infants to fall into a coma and die.
Alternatively, symptoms may not develop until later in childhood in some individuals with CPS, ASS, ASL or NAGS. In these cases, there is usually some remaining enzyme activity, ammonia levels are not as high as in the early-onset variant and the disease manifestations are not immediately life-threatening. These children normally have a history of nausea after eating high-protein foods, or of periods of irritability, hyperactivity, frequent vomiting and extreme tiredness.
In some, for example those with relatively mild disease or females with OTC, the disease remains hidden until adulthood. A history of disliking protein-rich foods, vomiting, periodic unusual behaviour and symptoms of mental illness may be the only clues that a problem exists.
For both categories of late-onset urea cycle disorders, illness, fever, accidents, surgery or certain medications can trigger a ‘crisis’ in which ammonia levels in the blood rapidly increase, bringing the risk of brain damage and coma. The crises are due to the body breaking down stored proteins, causing toxic ammonia to accumulate in the blood. Symptoms of high ammonia levels include hallucinations, sleep disorders, delusions and vomiting.
ARG is different from the other urea cycle disorders as its symptoms develop much more slowly. Individuals rarely have raised ammonia levels and the main disease features are delayed development, reduced growth, abnormal muscle tone (spasticity) and tremor.
Diagnosis of urea cycle disorders can be difficult and infants with the early-onset form are frequently misdiagnosed as suffering from severe infection. The characteristic finding in those with urea cycle disorders is that of high ammonia levels in the blood plus a normal blood glucose level and normal anion gap. An anion gap is simply a measure of various biochemical substances in the blood.
Amino acid analysis of the blood helps pinpoint the precise disorder, as can measuring the level of an acid called orotic acid. Additionally, liver samples may be taken to assess the activity of specific enzymes from the urea cycle. DNA tests confirm the diagnosis by identifying the genetic mutation at fault. Finally, magnetic resonance imaging (MRI) and computed tomography (CT) can help determine the degree and type of brain damage.
Management of urea cycle disorders comprises dietary manipulation to reduce the protein load, and therefore the burden on the urea cycle, and treatment to reduce the levels of ammonia in the blood.
A diet is prescribed that is sufficiently low in protein to avoid excessive ammonia production but high enough to sustain proper growth and development in children. Several low-protein products are available to help achieve this goal. The balance of protein, carbohydrates and fat must ensure that adequate calories are ingested, to protect against the body breaking down its own sources and therefore creating more ammonia. The balance must be adjusted over time to reflect children’s changing nutritional needs. This reduced-protein diet needs to be continued indefinitely and must be closely monitored by a dietician. Alongside the diet, specially formulated powders containing a balanced mix of essential amino acids are given, to avoid malnutrition of these important elements. In some cases, amino acids such as arginine or citrulline are supplemented, depending on the urea cycle disorder.
Multiple vitamin and calcium supplements are also recommended.
During periods of illness, fasting and infection, aggressive treatment is initiated to prevent the body breaking down its own energy stores. This comprises limiting protein intake and giving glucose and additional fluids. Sufferers are advised to avoid long periods of fasting; for example, by eating a snack at bedtime to reduce the period of overnight fasting.
Ammonia-reducing treatments include arginine chloride, which blocks the production of ammonia, and nitrogen-scavenging drugs (sodium phenylacetate, sodium phenylbutyrate and sodium benzoate), which ‘mop up’ the nitrogen and prevent it from being turned into ammonia. Dialysis is useful particularly where ammonia levels are significantly elevated. In some patients, liver transplantation may be required.
There is no cure for the urea cycle disorders. Early diagnosis and appropriate treatment of urea cycle disorders are often critical as even individuals with milder disease are at risk of permanent brain damage, coma and death if left untreated.
Sulphite oxidase deficiency is an extremely rare inherited disease in which incorrect ‘metabolism’ or processing of the amino acids methionine and cysteine leads to accumulation of their by-products in the blood and tissues. These products cause severe mental retardation, physical deformities and progressive brain damage.
Amino acids such as methionine and cysteine are the building blocks of proteins. After eating proteins, the body breaks them down into amino acids. Animal proteins include dairy products, meat, eggs and fish. Proteins are also found in plants including soy, legumes, grains and nuts. The body uses the amino acids to make its own proteins essential for life – for example enzymes; structural proteins in muscles, hair, skin, cells and cartilage; proteins that generate movement in muscles; or those involved in cell functioning or immune responses. In periods of fasting or illness, the body often switches to use its own proteins, and stored fats, to generate energy. Methionine is present in both animal and plant proteins, especially sesame seeds, nuts, spinach, mushrooms, broccoli, potatoes, fish and meat. Cysteine is found in most high-protein foods including meat, milk, eggs, red peppers, onions, broccoli and oats.
Sulphite oxidase is an enzyme that resides in the mitochondria, the energy-producing machinery inside cells. The enzyme is required for proper metabolism of methionine and cysteine.
Only around 50 cases of sulphite oxidase deficiency have been reported worldwide.
Both males and females have been affected in equal proportions.
Sulphite oxidase deficiency is linked to a genetic mutation that causes a defect either in the sulphite oxidase enzyme itself or, more commonly, in the helper or ‘co-factor’ molecule known as molybdenum co-factor. Since methionine and cysteine cannot be metabolised correctly, toxic by-products are left within the body that wreak havoc on Sulphite oxidase deficiency is linked to a genetic mutation that causes a defect either in the sulphite oxidase enzyme itself or, more commonly, in the helper or ‘co-factor’ molecule known as molybdenum co-factor. Since methionine and cysteine cannot be metabolised correctly, toxic by-products are left within the body that wreak havoc on the central nervous system. The exact mechanism by which this damage occurs has not been defined.
Sulphite oxidase deficiency is a recessively inherited genetic disorder, meaning that a child would only have the condition if both parents ‘carry’ the genetic mutation. Genes are arranged in structures called chromosomes that contain two strings or ‘alleles’. Offspring inherit one allele from their father and one from their mother. Carrying one copy of the mutated gene does not affect health, but when two mutated copies come together, the linked enzyme is deficient either in quantity or effect and the disease is expressed. For each and every pregnancy, there is a 1 in 4 chance of two carriers of the genetic mutation having a child with the disease.
Symptoms and signs of sulphite oxidase deficiency usually appear in infancy. In this scenario, severe seizures begin in the first days or weeks of life, which are hard to treat. The infant shows feeding problems, abnormal muscle tone, muscle twitching and signs of severe brain damage. Abnormal tightening of the muscles or ‘spasticity’ in the spinal column pulls the spine, neck and head into a backward arch shape. The prognosis is extremely poor, and many infants with sulphite oxidase deficiency lose their life to the disease. For those who survive, severe mental retardation is common. Furthermore, the eyes may show a lack of response to light and the lens of the eye can become dislocated.
In some individuals, the disease presents later in infancy or childhood. Individuals with this later-onset variation of sulphite oxidase deficiency potentially show less severe symptoms. For example, they may lose previously acquired milestones, such as being able to walk unaided or grasp objects, or can develop movement disorders. The outcome is thought to be better in this variant, although more research is needed to properly define the disease.
Children and infants with sulphite oxidase deficiency tend to have characteristic facial features comprising a narrow face diameter with deep-set eyes.
Blood and urine tests are normally the first investigations to be carried out when a diagnosis of sulphite oxidase deficiency is suspected. The most indicative are blood and urine tests to detect methionine and cysteine metabolites and a urine test to detect sulphite. Assessment of enzyme and co-factor levels is also revealing. Computed tomography (CT) and magnetic resonance imaging (MRI) can help evaluate the degree and type of brain damage.
Since there are so few cases of sulphite oxidase deficiency, little is know about how best to treat the condition.
For those with late-presenting disease, there may be some benefit from a diet that restricts protein in general and methionine and cysteine specifically. The diet needs to be continued indefinitely and must be initiated only after consultation with a dietician. As with any restrictive diet, it is important to ensure optimal nutrition. While natural protein intake is limited, a formula free of methionine and cysteine is prescribed. The specially formulated powder is designed to meet the nutritional needs of children at different ages. It contains a balanced mix of essential and non-essential amino acids, vitamins, minerals and carbohydrates to avoid malnutrition of other amino acids and to sustain normal growth and development in children. Several low-protein food products are also available.
Various drug treatments have been tried, although no definitive treatment can be recommended. For example, trimethylglycine or ‘betaine’ can be prescribed as this helps to metabolise cysteine, thus reducing levels of this amino acid in the body. However, this treatment is not suitable for infants. Similarly, thiamine (vitamin B1) supplementation may also be beneficial since this vitamin is low in sulphite oxidase deficiency.
Isovaleric acidaemia is an inherited condition in which abnormal metabolism of the amino acid leucine causes the fatty acid isovaleric acid to build up in the blood and urine.
Amino acids are the building blocks of proteins. After eating proteins, the body ‘metabolises’ or breaks them down into amino acids. Animal proteins include dairy products, meat, eggs and fish. Proteins are also found in plants including soy, legumes, grains and nuts. The body uses the amino acids to make its own proteins essential for life – for example enzymes; structural proteins in muscles, hair, skin, cells and cartilage; proteins that generate movement in muscles; or those involved in cell functioning or immune responses. In periods of fasting or illness, proteins in the body can be broken down to generate energy. Leucine is an essential amino acid meaning that it is not made by the body. Therefore, this amino acid comes from ingested protein or from the breakdown of previously ingested and stored proteins. Foods with a high-leucine content include beef, fish, chicken, soy beans, lentils and nuts.
Similarly, fatty acids are the building blocks of fats used by our bodies for energy.
Isovaleric acidaemia (-aemia meaning ‘in the blood’) is also known as isovaleric aciduria (-uria meaning ‘in the urine’) or isovaleric acid CoA dehydrogenase (IVD) deficiency, which describes the enzyme deficiency at its root.
Accumulation of isovaleric acid damages the brain and nervous system, leading to learning problems, seizures and loss of movement or ‘motor’ ability. The condition is closely related to maple syrup urine disease.
This rare condition is seen in up to 1 in 50,000 children. The condition affects males and females and different races equally.
The cause of isovaleric acidaemia is a mutation in the gene that codes for the enzyme isovaleryl CoA dehydrogenase. This enzyme is needed to metabolise leucine correctly. In individuals with isovaleric acidaemia, the enzyme is missing or functions poorly so the multi-step processing stops after the production of isovaleric acid. This fatty acid cannot be further processed so levels increase progressively.
Isovaleric acidaemia is a recessively inherited genetic disorder, meaning that a child would only have the condition if both parents ‘carry’ the genetic mutation. Genes are arranged in structures called chromosomes that contain two strings or ‘alleles’. Offspring inherit one allele from their father and one from their mother. Carrying one copy of the mutated gene does not affect health, but when two mutated copies come together, the linked enzyme is deficient either in quantity or effect and the disease is expressed. For each and every pregnancy, there is a 1 in 4 chance of two carriers of the genetic mutation having a child with isovaleric acidaemia.
There are two distinct patterns of symptoms in isovaleric acidaemia – either serious and typically life-threatening (acute), or long-standing and less severe (chronic).
Acute isovaleric acidaemia manifests in the first days of life, with pronounced accumulation of acidic metabolic products (metabolic acidosis). Infants may shake and tremble and their body temperature may be lower than normal. Severe symptoms of poor feeding, vomiting and tiredness progress to seizures and sometimes coma. Many infants do not survive such acute episodes.
In the chronic form, repeated attacks of metabolic acidosis are seen throughout life, in which acidic metabolites known as ketones accumulate in blood, tissues and urine. The events are triggered by infections, periods without food or through eating too much protein, and are due to the body breaking down stored proteins. During attacks, individuals experience vomiting, lack of appetite and extreme tiredness. They also emit an odour similar to that of sweaty feet.
This is a distinctive feature of isovaleric acidaemia and is a direct result of high levels of isovaleric acid. Between episodes, individuals are usually symptom free. Attacks may be common in infancy and early childhood but their frequency usually diminishes with increasing age. The severity of chronic isovaleric acidaemia varies between individuals. Some show no permanent signs while in others there may be delayed development and/or poor growth.
The characteristic odour during periods of illness helps to guide the diagnosis of isovaleric acidaemia. Diagnosis is usually confirmed through blood and urine tests that detect high levels of isovaleric acid. Genetic testing may also be used to identify the genetic abnormality and enzyme assays can assess levels of enzyme activity.
In some countries, routine newborn screening identifies sufferers.
The mainstay of treatment is a leucine-restricted diet to reduce the levels of isovaleric acid in the body. This diet needs to be continued indefinitely and must be initiated only after consultation with a dietician. To avoid malnutrition of other amino acids, children should be given a leucine-free formula. These specially formulated powders contain a balanced mix of essential and non-essential amino acids, vitamins and minerals, with minimal carbohydrates. Products are available for children of all ages.
Oral carnitine and glycine supplements are useful as these molecules bind to isovaleric acid and nullify its toxic effects. However, aspirin must not be taken by children receiving these supplements since aspirin interferes with their action.
Infections and fevers are treated aggressively to prevent muscle breakdown and subsequent release of stored proteins. This is achieved by limiting dietary protein during periods of illness and increasing the intake of carbohydrates. A range of special low-protein food products is available. The dose of carnitine is also increased at these times.
No cure exists for isovaleric acidaemia. However, early identification and intervention are effective, with many individuals showing normal development if the recommended treatment is maintained and acute attacks are well managed.
Glutaric aciduria means ‘glutaric acid in the urine’. This inherited metabolic condition is also known as glutaric acidaemia – or ‘glutaric acid in the blood’. It normally manifests in infancy and early childhood. There are two distinct forms.
In type I glutaric aciduria, abnormal processing or ‘metabolism’ of lysine, hydroxylysine and tryptophan generates toxic by-products that cause severe brain damage. Lysine, hydroxylysine and tryptophan are amino acids – the building blocks of proteins. After eating proteins, the body breaks them down into amino acids. Animal proteins include dairy products, meat, eggs and fish. Proteins are also found in plants including soy, legumes, grains and nuts. The body uses the amino acids to make its own proteins essential for life – for example enzymes; structural proteins in muscles, hair, skin, cells and cartilage; proteins that generate movement in muscles; or those involved in cell functioning or immune responses. In periods of starvation, amino acids can be redirected to generate energy for the body. When lysine, hydroxylysine and tryptophan are not metabolised properly, intermediate breakdown products (glutaric acid, glutaryl-CoA, 3-hydroxyglutaric acid and glutaconic acid) accumulate in body fluids and brain tissue. The build-up of metabolites is especially pronounced when the body is under stress. Characteristically, between the ages of 6 and 18 months the child experiences a metabolic ‘crisis’. This sudden episode occurs during periods of illness or fever or after immunisation, lack of food or minor head injury. The crisis seems to be a turning point in the condition and triggers significant brain damage. The basal ganglia of the brain, which helps control movement, is most affected. In addition, the metabolites cause damage to other organs, although to a lesser extent. It is not known how glutaric acid and the other metabolites exert their destruction. The risk of crises diminishes as the child gets older.
Type II glutaric aciduria is linked to a deficiency in enzymes involved in processing fats and proteins. Partly metabolised fats and proteins accumulate in the body and cause the blood and tissues to become dangerously acidic. Like type I, metabolic crises triggered by common childhood illnesses or stress worsen the condition. In this scenario they trigger the body to break down its own stores of protein and fats thus generating the toxic by-products that cause the body harm. Liver and brain damage are characteristic.
The biochemical alterations in both types of glutaric aciduria can hamper the production of carnitine, a product of lysine metabolism important for generating energy from dietary fats.
Type I glutaric aciduria is rare. Prevalence studies are limited but suggest that the disease occurs in 1 in 40,000 Caucasian births, although a study in Sweden estimated an incidence of 1 in 30,000 births in its population. It is more common in genetically close communities such as the Ojibway Indian population in Canada or the Amish in the USA where the incidence may reach as many as 1 in 300 newborns. However, a tendency for misdiagnosis may mean that these figures underestimate the true frequency.
Type II glutaric aciduria is thought to be even more rare than its counterpart, although the precise incidence is not known.
Glutaric aciduria is a genetic disorder in which mutations in certain genes cause a deficiency or reduce the efficiency of certain enzymes. The enzymes are normally active in the mitochondria, which represent the energy-producing hub of cells.
In type I glutaric aciduria, the error occurs in the gene coding for the enzyme glutaryl-coenzyme A dehydrogenase (GCDH), which would normally metabolise lysine, hydroxylysine and tryptophan.
In type II disease, a deficiency is seen in either of two enzymes – enzyme electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH). Mutations in any of three genes can result in the deficiency, since the ETF enzyme has two sections each created by a separate gene. People with residual enzyme activity show milder symptoms, while severe disease develops in those in whom the enzyme is missing completely.
The conditions are recessive in nature, meaning that a child would only have the condition if both parents ‘carry’ the genetic mutation. Genes are arranged in structures called chromosomes that contain two strings or ‘alleles’. Offspring inherit one allele from their father and one from their mother. Carrying one copy of the mutated gene does not affect health, but when two mutated copies come together, the linked enzyme is deficient either in quantity or effect and the disease is expressed. For each and every pregnancy, there is a 1 in 4 chance of two carriers of the glutaric aciduria mutation having a child with the disease.
From birth, babies with type I glutaric aciduria have unusually large heads, due to abnormalities in brain development. Sufferers may be asymptomatic before a crisis, particularly if they eat a low-protein diet and have few illnesses. Or they may show only general symptoms such as irritability, abnormal muscle tone or feeding difficulties. In some, abnormal bleeding occurs in the brain or eyes. However, after a crisis has triggered brain damage, the child will show difficulty moving, spasms, jerking, rigidity or decreased muscle tone, weakness and a tendency for seizures. Head and body control may diminish and the suck and swallow reflexes may be lost. Prolonged muscle contractions make the arms and legs stiff, with twisting of the hands and feet. The symptoms, which vary in severity and worsen over time, show similarities to those of cerebral palsy. Intellectual function may be affected.
In type II disorder, metabolic crises cause weakness, poor feeding, reduced activity, nausea and vomiting. Blood sugar levels can drop dramatically after exercise causing severe weakness, shakiness, dizziness and difficulties breathing. The events triggered by a crisis can be life threatening. Again, the condition ranges in severity. In mild cases, children may be affected only during times of metabolic stress. Indeed, muscle weakness in adulthood may be the first sign. Those with more severe disease are born with brain malformations, an enlarged liver and heart, fluid-filled cysts in the kidneys, abnormalities in the kidneys and external genitals in males and unusual facial features. There is also a characteristic smell on the breath that resembles sweaty feet.
Diagnosis of this rare condition can be difficult. The disease is relatively silent and therefore not suspected unless a metabolic crisis occurs. The large head size in type I disease may be detected during routine infant screening and triggers further investigation. In some, abnormalities in biochemicals may be detected as part of routine neonatal screening. Post-crisis symptoms in type I are often mistaken for cerebral palsy. Unfortunately, abnormal bleeding is often misdiagnosed as the result of abuse in these children.
A blood or urine test for glutaric acid is a key diagnostic feature of glutaric aciduria. Furthermore, low levels of carnitine in the blood are characteristic and measuring the activity of the specific enzymes can support the diagnosis. Cranial ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) may be used to assess the presence and extent of neurological damage in type I glutaric aciduria. In type II disease, liver biopsies are useful to identify abnormal fat accumulations.
Screening siblings of children affected by glutamic aciduria facilitates early identification and intervention.
The mainstay of treatment for type I glutaric aciduria is dietary manipulation aimed at reducing the production of glutaric acid and other intermediate metabolites. The diet involves restricting the intake of natural protein and of lysine specifically. Tryptophan is reduced but not eliminated as this amino acid is important for producing serotonin – a chemical messenger in the brain. Lysine-rich foods include fish, meat and meat products, cow’s milk and dairy products, eggs, potatoes, soy, nuts, lentils and spinach. Tryptophan-rich foods include chocolate, oats, dairy products, bananas, mangoes, fish, meat and meat products. Such a diet must be managed carefully to avoid malnutrition in certain amino acids. It should strike a balance between the need for protein for growth versus its restriction for avoidance of adverse effects. This complex task should be undertaken only with the advice of a dietician. A generally low-protein diet is advised, alongside supplementation with lysine-free, low-tryptophan amino acid mixtures to ensure supply of the other amino acids essential for optimal health. The diet should include a high carbohydrate and fat content to provide sufficient calories. Adequate fluid levels should be maintained and vitamin and mineral intake optimised. The ability to process protein improves with age and the diet should be reviewed regularly to adapt to the changing nutritional needs of the children. A range of lysine-free and low-tryptophan formulas is available, designed specifically to meet the nutritional needs of children at different ages.
Since illness worsens the condition, therapy is intensified during these periods to prevent brain damage. This involves increasing carbohydrate and fat intake, temporarily ceasing all protein intake, increasing carnitine supplementation and monitoring the child closely.
After the crisis, the permanent brain injury becomes the focus of treatment, with intervention designed to reduce the frequency of seizures and prevent further deterioration. The anti-spasticity drug baclofen can reduce abnormal muscle tone and improve motor function to some degree. Benzodiazepines, which slow the central nervous system, are useful for treating seizures.
It is possible that use of special constraint seating can limit abnormal movements in type I glutaric aciduria. However, such occupational therapy may worsen the increased body tone and spasms. Aids that provide support in the upright position without constraint (such as baby bouncers that hang from door frames) may be more suitable and can reduce body rigidity in infants.
In type II glutaric aciduria, a low-protein and low-fat diet is advised. A small quantity of protein and fat are needed, but carbohydrates should deliver the majority of calories for energy and growth. Again, a dietician should be consulted. The child should drink additional fluids during periods of illness to combat the rising levels of glutamic acid. Also, protein should be excluded and energy-rich food such as sugar-based snacks should be eaten to prevent the body needing to use its own stores of protein.
In both types, carnitine depletion is treated with oral carnitine supplements, although these may not raise carnitine levels in muscle. Regular intravenous carnitine replacement could be more effective. The vitamin riboflavin may be given to increase carnitine levels and promote improved growth and greater muscle strength. Multivitamin and mineral supplements are also advised. In type II disease, choline supplements are useful to increase exercise capacity and tone in the trunk and improve general well-being.
Treatment, particularly diet modification, is effective in both types of glutaric aciduria. Hence, early diagnosis of this rare metabolic disease is essential. This is most acute in type I disease where early intervention can reverse many of the pre-crisis symptoms and may provide some protection against brain damage in the event of a crisis.
Methylmalonic acidaemia is a genetically inherited disease in which the body is unable to process certain amino acids and fats correctly. This leads to the accumulation of a molecule called methylmalonyl-CoA and other by-products in the blood, which poison the body and brain. Methylmalonyl-CoA is a form of methylmalonic acid. Methylmalonic acidaemia (-aemia = in the blood) is also known as methylmalonic aciduria (-uria = in the urine) since high levels of methylmalonyl-CoA are also excreted in the urine. The disease shows many similarities to propionic acidaemia.
There are several variants of methylmalonic acidaemia, which range in severity from mild to life threatening. Seizures and progressive brain damage are common. Stroke, due to abnormal blood flow to the brain, and coma are two other serious complications. Untreated, the prognosis is poor.
The main amino acids involved are isoleucine, valine, threonine and methionine. Amino acids are the building blocks of proteins. After eating proteins, the body ‘metabolises’ or breaks them down into amino acids. Animal proteins include dairy products, meat, eggs and fish. Proteins are also found in plants including soy, legumes, grains and nuts. The body uses the amino acids to make its own proteins essential for life – for example enzymes; structural proteins in muscles, hair, skin, cells and cartilage; proteins that generate movement in muscles; or those involved in cell functioning or immune responses. In periods of fasting or illness, the body often switches to use its own proteins, and stored fats, to generate energy. Isoleucine, valine, threonine and methionine are essential amino acids meaning that the body cannot make them. Therefore, these amino acids come from ingested protein or from the breakdown of previously ingested and stored proteins.
Methylmalonic acidaemia is estimated to occur in 1 in 25,000 to 48,000 individuals globally. The condition affects both sexes equally.
Most commonly, methylmalonic acidaemia arises from a genetic mutation that limits the quantity or functioning of an enzyme called ‘methylmalonyl-CoA mutase’. This enzyme is involved in the metabolism of certain amino acids and fats. Alternatively, the mutation may be in genes that code for cobalamin (vitamin B12), which is a metabolic co-factor or ‘helper’ for methylmalonyl-CoA mutase. Individuals with the co-factor deficiency have a better prognosis than those in whom the methylmalonyl-CoA mutase is missing or reduced in activity.
Methylmalonic acidaemia is a recessively inherited genetic disorder, meaning that a child would only have the condition if both parents ‘carry’ the genetic mutation. Genes are arranged in structures called chromosomes that contain two strings or ‘alleles’. Offspring inherit one allele from their father and one from their mother. Carrying one copy of the mutated gene does not affect health, but when two mutated copies come together, the linked enzyme is deficient either in quantity or effect and the disease is expressed. For each and every pregnancy, there is a 1 in 4 chance of two carriers of the genetic mutation having a child with the disease.
Although various forms of methylmalonic acidaemia exist, each with a specific profile of symptoms, they share the feature of intermittent metabolic attacks or ‘crises’. The crises are triggered by infections, fever and periods without food, and are due to the body breaking down stored proteins and fats and releasing the toxic substances into the blood. During attacks, metabolic acidosis occurs where the blood and tissues become abnormally acidic due to pronounced accumulation of metabolic products. Keto acids also build up in the blood and tissues causing ketoacidosis, and spill over to the urine. Keto acids are metabolic by-products created when the body resorts to using its own protein and fat stores for energy.
The most severe form of methylmalonic acidaemia is seen in very young infants. Although healthy at birth, within the first 1 to 2 weeks of life infants show poor feeding, extreme tiredness, vomiting, floppiness, weak muscle tone and signs of brain damage. Metabolic acidosis and ketoacidosis are severe and high blood levels of ammonia, a waste product of protein breakdown, and the amino acid glycine can be detected. Infants with this form rarely survive.
Less severe forms of methylmalonic acidaemia appear slightly later in infancy or in early childhood. In addition to feeding problems, vomiting, extreme tiredness and failure to thrive, individuals may suffer seizures and stroke; the latter potentially causing permanent movement disorder. There may be noticeable developmental delay, learning difficulties or intellectual impairment. The liver and spleen may be enlarged and kidney disease can develop. The immune system is often impaired, making the children susceptible to infections. In some individuals, there may be reduced vision and damage to the lining at the back of the eye.
Several tests are used to arrive at a diagnosis and to assess the severity of methylmalonic acidaemia. In some countries, newborn screening programmes help detect the condition early.
Blood and urine tests showing high levels of methylmalonic acid are the main diagnostic indicator. Other non-specific tests include detecting signs of ketoacidosis and metabolic acidosis and high levels of ammonia and glycine in the blood. Enzyme analysis and genetic testing are also useful to establish the form of methylmalonic acidaemia. Computed tomography (CT) and magnetic resonance imaging (MRI) can help evaluate brain damage.
Treatment of methylmalonic acidaemia involves dietary modification to restrict the intake of isoleucine, valine, threonine and methionine. The diet needs to be continued indefinitely and must be initiated only after consultation with a dietician.
As with any restrictive diet, it is important to ensure optimal nutrition for growth and development. While natural protein intake is limited, a formula free of isoleucine, valine, threonine and methionine is prescribed. A range of such formulas is available, designed specifically to meet the nutritional needs of children at different ages. These specially formulated powders contain a balanced mix of essential and non-essential amino acids, vitamins, minerals and carbohydrates to avoid malnutrition of other amino acids and to sustain normal growth in children. Several low-protein food products are also available.
During periods of illness, fasting and infection, aggressive treatment is initiated to prevent the body breaking down its own energy stores. This comprises limiting protein intake, giving glucose and additional fluids, increasing carnitine supplementation plus, in some cases, using dialysis to reduce ammonia levels and correct metabolic acidosis.
Vitamin B12 supplementation helps to improve metabolic control and reduce the risk of complications in those with a deficiency in this co-factor. Supplementation with carnitine (an enzyme involved in fatty acid metabolism) helps to neutralise the toxic metabolic by-products. Antibiotics may help to lower the amount of methylmalonic acid produced within the body. Kidney and/or liver transplantation may also be necessary for some.
Sufferers are advised to avoid long periods of fasting. For example, by eating a snack at bedtime, the period of overnight fasting can be reduced.
Methylmalonic acidaemia is typically a serious condition, with potentially devastating consequences. Early and appropriate intervention helps to reduce the risk of complications. However, even with treatment some individuals develop permanent learning difficulties, kidney failure and movement disorders.
The content provided by shs-nutrition is for information purposes only and is in no way intended to be a substitute for medical consultation with your doctor, dietitian or healthcare professional. The information, opinions, and recommendations presented in these pages are not intended to replace the care of your own doctor, dietitian or healthcare professional. Before you make any changes in the management of your diet / treatment or any other persons diet /treatment you should always consult your doctor, dietitian or healthcare professional. Although we carefully review our content, shs-nutrition cannot guarantee or take responsibility for the medical accuracy of documents we publish, nor can shs-nutrition assume any liability for the content of any web site linked to our site. © 2008 SHS International. All rights reserved.
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