Isovaleric Acidaemia

What else is it called?

  • Isovaleric acid-CoA dehydrogenase deficiency 
  • Isovaleryl-CoA dehydrogenase deficiency 
  • IVA 
  • IVD deficiency 

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What causes it?

Isovaleric Acidaemia is caused by a problem in the IVD gene. This gene produces an enzyme which breaks down an amino acid called leucine. This process is needed because leucine is a part of many proteins which helps to provide energy to your body. 

If you have a problem in the IVD gene, you will not produce enough of this enzyme. Therefore, you will be unable to break down leucine properly and this causes its compounds to build up to toxic levels. This can damage your brain and your nervous system, leading to a number of serious health issues. 

 

How common is it?

Isovaleric Acidaemia is a very rare disorder. The amount of cases is difficult to estimate because some people with the disorder do not have any symptoms. It is estimated to affect 1-9 in every 100,000 people. In the USA, at least 1 in 250,000 people have the disorder. 

There are currently no figures for the prevalence of Isovaleric Acidaemia in the UK. 

 

What are the signs and symptoms?

Isovaleric Acidaemia presents differently in different people, and symptoms are not necessarily the same for everybody. Also, whilst some people never show any symptoms (asymptomatic) or have very mild signs of the disorder, others experience Isovaleric Acidosis as a life-threatening condition.   

The signs described here are typical of most people with the disorder. Symptoms usually appear in the first few days of life and can include: 

  • Poor feeding 
  • Vomiting 
  • Seizures 
  • Lack of energy (lethargy) 
  • A “sweaty feet” smell, especially during periods of illness 

Later symptoms may also include not gaining weight or growing as expected (failure to thrive), and delayed development. 

Without adequate treatment, symptoms can worsen and progress into more serious health issues, causing repeated seizures, comas and, in extreme cases, death. It is important to follow the information of your medical team in order to reduce the likelihood of these symptoms occurring. However, sometimes symptoms will worsen with no explanation. Should this happen, seek help immediately. 

In some cases, the symptoms of the disorder may appear to come and go during childhood. 

Many people with Isovaleric Acidaemia are able to manage it well and live healthy lives. However, in the most severe cases, even when treatment is followed carefully, seizures and comas can occur and cause damage that leads to intellectual or learning disabilities. 

How is it diagnosed?

Isovaleric Acidaemia is diagnosed using a specialised blood test. Genetic testing will be required to confirm the diagnosis. 

Children in the UK are offered a blood spot screening (also known as the heel prick test), usually at 5 days old. This involves taking pricking their heel to take spots of blood that are tested for a variety of different genetic disorders, including Isovaleric Acidaemia. The majority of cases are identified in this way. 

Some people receive a diagnosis later in childhood because they have a milder form of the disorder. Regular check-ups and treatment are still important to reduce health risks. 

Can it be treated?

There is no cure for Isovaleric Acidaemia, however there are a range of ways that the disorder can be managed successfully, and plans can be put in place to reduce the chances of the disorder getting worse. 

One of the most important ways to manage the disorder is through following a specific diet. It is recommended that you follow a low-protein diet, as people with Isovaleric Acidaemia are unable to process protein properly. A specialised dietitian will help to develop an appropriate diet plan for you. It is important that you speak to your dietitian before making any changes to your food intake so that they can help you to make informed, healthy choices. 

It is likely that you will be told to ensure that you eat at regular intervals and avoid fasting. This is to ensure that your body has a consistent source of energy to function properly. 

If you do not follow your dietary advice, or you have long periods without eating, you may experience a metabolic crisis. Symptoms include:  

  • Vomiting and an inability to keep food down 
  • Lack of energy 
  • Irritability 
  • Breathing difficulties

Metabolic crisis is caused by inadequate or inappropriate diet intake and can be fatal if ignored. It can also be triggered by illness. You will be given an emergency treatment plan to implement at home in times of metabolic crisis. However, this may include attending hospital if the symptoms do not improve quickly. Speak to your medical team to discuss an emergency treatment plan that is suitable for you. 

Although many people with this disorder will live a healthy life, this is increased by an early diagnosis and careful adherence to the treatment plan that your medical team give you. However, some people with more severe cases of Isovaleric Acidaemia may experience repeated metabolic crises, despite following their treatment plans. This can increase the likelihood of damage to the brain and cause learning difficulties or intellectual disabilities. 

Do my family need to be tested?

Isovaleric Acidaemia is inherited from both parents in an autosomal recessive inheritance pattern. This means that both parents are carriers of the disorder through their genes.  

All genes come in pairs. Carriers of Isovaleric Acidaemia have one working IVD gene and one faulty gene. Children inherit one gene from each parent to make their pair. Whether you have Isovaleric Acidaemia depends on the genes you inherit: 

  • There is a 50% chance that the child will inherit one faulty and one working gene, which means they will also be a carrier. 
  • There is a 25% chance that the child will inherit two working genes and not inherit or carry the faulty gene. 
  • There is a 25% chance that the child will inherit two faulty genes, which means they will have Isovaleric Acidaemia. 

If you think you, or somebody in your family, may have Isovaleric Acidaemia, or that you may be a carrier, contact your medical team who may refer you for genetic testing. 

 

Relevant Organisations

References

References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing helen@metabolicsupportuk.org [Resource Library No: AAP002]. 

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