Isovaleric acidaemia is a genetic, metabolic condition and a type of organic acid disorder.¹ People with isovaleric acidaemia cannot properly break down leucine. Leucine is an amino acid (protein building block) that is found in many foods and is broken down by the body to produce energy.² When leucine is not broken down properly, this can lead to a build-up of isovaleric acid and its by-products, which are toxic to the body.

Symptoms can appear early in life or later in childhood, and may include low muscle tone (hypotonia), extreme tiredness and lack of energy (lethargy), poor appetite, vomiting, as well as an odour (smell) like sweaty feet.^1-4 If left untreated, this can lead to coma and early death. Children may have failure to thrive (does not gain enough weight or grow as expected for that age), developmental delay, intellectual disability, epilepsy and movement disorders. There are also individuals who may not have any symptoms (asymptomatic).^2,3

In Australia, isovaleric acidaemia is often detected shortly after birth via newborn bloodspot screening (NBS) programs. Additional testing is required for a diagnosis. For individuals who are not screened at birth, isovaleric acidaemia is often diagnosed after symptoms develop. Early diagnosis and treatment can help to prevent life-threatening and long-term complications.⁴

Synonyms:² IVA; Isovaleric acid CoA dehydrogenase deficiency; Isovaleric aciduria

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:33 Isovaleric acidemia

ICD-11: 5C50.E0 Classical organic aciduria

Symptoms of isovaleric acidaemia vary widely between individuals and may differ in terms of age of onset (when the symptoms present) and severity of symptoms.^3-6

Some individuals may develop acute, early symptoms within the first few days of life; in some cases, this can occur before the condition is detected by newborn screening programs.⁴ Symptoms can also develop after the newborn period for some individuals.

Individuals may develop metabolic crisis, characterised by ketosis (increased ketone levels), metabolic acidosis (too much acid in the blood), increased levels of lactate, and hyperammonaemia (elevated ammonia levels in the blood).^4-6 Metabolic crises are often brought on (triggered) by fasting, illness or high protein intake. Symptoms may present as low muscle tone (hypotonia), extreme tiredness and lack of energy (lethargy), poor appetite or feeding, vomiting, a characteristic odour (smell) of sweaty feet and movement disorders. If left untreated, the metabolic crisis can lead to seizures, coma and early death.

Individuals with isovaleric acidaemia may have delayed growth, developmental delay and intellectual disability. They may also have thrombocytopenia (low platelet count), neutropenia (low levels of neutrophils, a type of white blood cells), pancytopenia (low levels of red blood cells, platelets and neutrophils) and hypocalcemia (low level of calcium in the blood).^3-6

Early diagnosis and appropriate management of isovaleric acidaemia, particularly before symptoms develop, can prevent or reduce frequency of metabolic crises, and its long-term effects. Management of isovaleric acidaemia before symptoms develop can increase the chance of a child with isovaleric acidaemia growing and developing in a similar way to their healthy peers who don’t have isovaleric acidaemia.^3-6

There may also be individuals who do not present with any symptoms (asymptomatic).^2,3

Please speak to your medical team to learn more about the symptoms of this condition.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

Isovaleric acidaemia is a genetic condition. It is caused by disease-causing genetic changes (variants) in the IVD gene on Chromosome 15.^3,4 The IVD gene is responsible for producing an enzyme called isovaleryl-CoA dehydrogenase (IVDH) that is involved in breaking down leucine.

All individuals have two copies (alleles) of the IVD gene – one copy inherited from each parent. Isovaleric acidaemia is an autosomal recessive condition,^3,4 which means both copies of the IVD gene must have the disease-causing genetic variants. More information on autosomal recessive inheritance pattern can be found at Centre for Genetics Education: Autosomal recessive inheritance.

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Newborn screening

In Australia, isovaleric acidaemia is usually detected via the newborn bloodspot screening (NBS) programs.  Shortly after birth and with parental consent, a nurse or midwife will collect the baby’s blood via a heel prick blood test. The healthcare provider will then send it to a specific laboratory to test for a range of rare conditions, including isovaleric acidaemia. If the test results suggest that there is a risk of the baby having one of the screened conditions, laboratory staff will promptly get in touch with healthcare providers. The healthcare providers will then arrange for the baby to have further testing to confirm if the baby actually has the condition. The healthcare providers will also organise for the baby to receive urgent care if required. Depending on your state or territory, parents may or may not receive a notification if the test results are clear. You can find out more about NBS in your state or territory at Australian Government Department of Health, Disability and Ageing: Delivering newborn bloodspot screening programs.

Newborn bloodspot screening is a reliable way to check for certain rare conditions early in life. Although it’s extremely rare, cases can sometimes be missed. If you are concerned your baby may have a condition that they have already been screened for, you should contact a medical professional.

Diagnosis

A diagnosis of isovaleric acidaemia may be suspected based on an abnormal result from NBS but additional tests or a clinical examination will be required to confirm a diagnosis. For individuals who are not screened at birth, isovaleric acidaemia is often diagnosed after symptoms develop.

Diagnosis of isovaleric acidaemia may be made based on clinical evaluation of symptoms, laboratory tests that detect for increased level of isovalerylcarnitine (as C5-carnitine) in blood and organic acids in the urine, and confirmed by genetic testing.^3,4

As part of the diagnostic process, doctors may do a differential diagnosis, which is to rule out other conditions that have similar symptoms, such as other organic acidaemias, urea cycle disorders and sepsis.³

Please speak to your medical team to learn more about the available pathways for diagnosis of this condition.

There is currently no curative treatment for isovaleric acidaemia; however early diagnosis and appropriate management, particularly before symptoms develop, can help ensure better overall outcomes.^3-6 Management of isovaleric acidaemia before symptoms develop can increase the chance of a child with isovaleric acidaemia growing and developing in a similar way to their healthy peers who don’t have isovaleric acidaemia.

Management of isovaleric acidaemia involves a low protein diet (to manage intake of leucine) and a special nutritional supplement, together with regular blood tests to detect for deficiencies in essential amino acids.^3-5  The recommended amount of protein from food and supplement varies between individuals – this depends on an individual’s leucine tolerance, which may also change over time, and should be monitored and tailored by a metabolic dietician. Carnitine supplementation, and in some cases glycine supplementation, is also used to help the body remove the toxic byproducts that build up in isovaleric acidaemia.

Metabolic crisis is a medical emergency and requires immediate treatment. More information about recommended emergency treatment for isovaleric acidaemia, including in times of illness (which can be a trigger of metabolic crisis) can be found at Practical considerations for the diagnosis and management of isovaleryl-coA-dehydrogenase deficiency (isovaleric acidemia): Systematic search and review and expert opinions.

Management of symptoms may include management of movement disorders, tube feeding, physiotherapy, occupational therapy, speech therapy, and other therapies.^4,5

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities. For many rare diseases, treatment options may be limited. Participation in a clinical trial may provide access to new or emerging therapies.

Healthcare professionals involved in the clinical care of individuals with isovaleric acidaemia may include general practitioners (GP), paediatricians, metabolic physicians, genetic counsellors, metabolic dietitians, neurologists, haematologists, physiotherapists, occupational therapists, speech therapists and others. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.  It is recommended that care is overseen by a metabolic specialist team.⁴

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

This may not be applicable to all rare diseases but for many, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

The following additional guidance is available from international experts outside Australia; however, there may be information that is not relevant or applicable to the Australian context:

• Practical considerations for the diagnosis and management of isovaleryl-coA-dehydrogenase deficiency (isovaleric acidemia): Systematic search and review and expert opinions was published in 2025 and includes 15 statements on the presentation, diagnosis, management, and outcome of IVA, based on available scientific evidence and consensus-derived expert conclusions; these statements were aimed to serve as a basis for more standardised care for IVA.⁵

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

In addition, individuals, their parents, families and carers often develop extensive expertise on their specific rare disease. It is important to recognise that they can contribute valuable knowledge about their rare condition. Rare diseases often impact individuals differently, so it’s important to consider a person’s lived experience.

Below are some considerations for the emergency management of individuals living with isovaleric acidaemia, including when presenting to emergency departments:⁴

• Prolonged fasting as well as excess of dietary protein or protein malnutrition should be avoided.
• Individuals are at risk of metabolic crises and acute encephalopathic crisis, particularly during times of illness and fasting. Emergency treatment will be required.
• Metabolic specialist team or specialists with expertise in inherited metabolic disorders to be consulted for emergency surgeries and procedures in respect to perioperative fluid and nutritional management.

Practical considerations for the diagnosis and management of isovaleryl-coA-dehydrogenase deficiency (isovaleric acidemia): Systematic search and review and expert opinions include a section on emergency treatment, which covers acute measures, laboratory tests to monitor emergency treatment, sick day management at home, and perioperative management.

Metabolic Dietary Disorders Association (MDDA): Latest Research Updates has information about key areas of ongoing research for various inborn errors of metabolism conditions, including organic acidaemias.

Australian Organisation:

Metabolic Dietary Disorders Association (MDDA)
Website: https://mdda.org.au/

Metabolic Dietary Disorders Association Inc (MDDA) is the national peak consumer body dedicated to supporting, educating, connecting, and representing all individuals their families and carers living with Inborn Errors of protein Metabolism (IEpM).

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

Isovaleric acidaemia varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

The ASIEM Low Protein Handbook for Organic acid disorders

Organic Aciduria Fruit and Veg Counting Lists

Organic Aciduria General Protein Counting Lists

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information relevant to isovaleric acidaemia can be found at:

• Government of Western Australia Department of Health: Isovaleric acidaemia (IVA)
• Metabolic Dietary Disorders Association (MDDA): Isovaleric Aciduria (IVA)
• Genetic and Rare Diseases (GARD) Information Center: Isovaleric acidemia
• National Organization for Rare Disorders (NORD): Isovaleric Acidemia

Orphanet: Isovaleric acidemia

GeneReviews^®:Classic Isovaleric Acidemia

Online Mendelian Inheritance in Man, OMIM^®: #243500 – Isovaleric acidemia; IVA

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team.

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