Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a genetic metabolic condition that affects the body’s ability to break down certain fats and turn them into energy. It is classified as a type of mitochondrial fatty acid oxidation disorder.¹

People with MCAD deficiency do not have enough functional MCAD enzyme.^2,3 The MCAD enzyme is a protein that is involved in converting a type of fat (medium-chain fats) into energy, which happens in the mitochondria (the energy powerhouse of cells in the body). This production of energy from the body’s fat stores usually occurs when the body needs more energy (increased energy demand), such as during illness or fasting.^2-5 People with MCAD deficiency struggle to produce energy from their body’s fat stores, which can lead to low blood sugar (hypoglycaemia) and metabolic crisis that can be life-threatening if not treated promptly.

In Australia, MCAD deficiency 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, MCAD deficiency is often diagnosed after symptoms develop. Early detection and management of MCAD deficiency is important to prevent long term damage and life-threatening complications.

Synonyms:¹ MCADD; ACADM deficiency; Medium chain acyl-coenzyme A dehydrogenase deficiency; Carnitine deficiency secondary to medium-chain acyl-CoA dehydrogenase deficiency

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:42 Medium chain acyl-CoA dehydrogenase deficiency 

ICD-11:5C52.01 Medium chain acyl-CoA dehydrogenase deficiency

Symptoms of MCAD deficiency are not seen at birth, but usually present within the first 2 years of life. This tends to correspond to when a baby starts sleeping longer and feeding less frequently during the night or when they have an infection that decreases appetite and increase their body’s energy demands.^1-4 In some cases, individuals may not develop obvious symptoms until adulthood, where symptoms may be brought upon by stress on the body such as an illness, surgery or excessive consumption of alcohol. Early diagnosis and appropriate management can help prevent the development of symptoms.

If left untreated, individuals with MCAD deficiency are at risk of having low levels of ketones and low blood sugar (hypoketotic hypoglycaemia) and metabolic crisis.^1-4 Symptoms may include extreme tiredness and lack of energy (lethargy), vomiting, and can progress to seizures, coma and early death if not treated promptly. They may also have an enlarged liver (hepatomegaly) and at risk of brain damage. 

There may be other complications that have not been mentioned here. Please speak to your medical team to learn more about the symptoms and complications 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.

MCAD deficiency is a genetic condition. It is caused by disease-causing genetic changes (variants) in the ACADM gene on chromosome 1. The ACADM gene is responsible for producing an enzyme called medium-chain acyl-CoA dehydrogenase (MCAD) that is involved in breaking down medium-chain fatty acids in the mitochondrial fatty acid β-oxidation pathway.^1-4

All individuals have two copies (alleles) of the ACADM gene – one copy inherited from each parent. MCAD deficiency is an autosomal recessive condition, which means both copies of the ACADM 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, MCAD deficiency 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 MCAD deficiency. 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 MCAD deficiency 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, MCAD deficiency is often diagnosed after symptoms develop.

Diagnosis of MCAD deficiency may be made based on clinical evaluation of symptoms, laboratory tests on blood and urine samples to detect for increased levels of specific acylcarnitines, and confirmed by genetic testing.^1,2,4

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 causes of a Reye-like syndrome (such as acute noninflammatory encephalopathy with hyperammonaemia, liver dysfunction, and fatty infiltration of the liver), other fatty acid disorders, urea cycle disorders, organic acidurias, defect in ketogenesis, respiratory chain defects and inborn errors of carbohydrate metabolism.⁴

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 MCAD deficiency; however, early diagnosis and appropriate management can help prevent or reduce development of symptoms, long-term effects, and the risk of life-threatening complications, including sudden death.

Management of MCAD deficiency is mainly aimed at avoidance of fasting (not going without food for a period of time) to prevent hypoglycaemia.^2,4 This may also involve frequent feeding, including overnight feeding, a bedtime snack or use of uncooked cornstarch as a source of complex carbohydrates at bedtime to ensure there is sufficient glucose supply during the night.⁴ The recommended maximum time between food may change with age. Management of the condition should be done in consultation with a metabolic dietitian to ensure a healthy, balanced diet suitable for the individual.²

Additional measures, such as glucose supplementation, may need to be taken during time of illness to prevent metabolic crisis. Hypoglycaemia and metabolic crisis are medical emergencies and should be treated promptly.

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 MCAD deficiency may include general practitioners (GP), paediatricians, geneticists, metabolic physicians, genetic counsellors, endocrinologists, metabolic dieticians, and other metabolic specialists and care team. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here. It is recommended that care be managed 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

If you know of any relevant clinical care guidelines, please let us know via the  Contribute page.

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

• Management Principles for Acute Illness in Patients With Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency is a clinical report intended to provide pediatricians in the United States of America with additional information regarding the acute clinical care of patients with MCADD; published in 2021.

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 MCAD deficiency, including when presenting to emergency departments:^3-4,6

• Individuals with MCAD deficiency are at risk of hypoglycaemia and metabolic crisis, which are medical emergencies and need to be treated promptly.
• Individuals with MCADD require immediate triage and medical attention in emergency departments as the condition can quickly progress to life-threatening stages. Individuals should be evaluated rapidly for signs and symptoms of hypoglyacemia, including mental status changes.
• Prolonged fasting should be avoided.
• metabolic specialist team to be consulted on emergency surgeries/procedures in regard to perioperative fluid & nutritional management.

Australian Organisation:

Mito Foundation
Website: https://www.mito.org.au

The Mito Foundation is the only organisation dedicated to supporting and empowering people impacted by mitochondrial disease (mito) in Australia. It provides resources and support services for people impacted by mito, and their families, while increasing awareness and understanding of this devastating disease. The foundation aims to transform outcomes for the mito community by driving meaningful change and funding essential research into the prevention, diagnosis, treatment and cures of mitochondrial disorders.

International Organisation:

FOD (Fatty Oxidation Disorders) Family Support Group (United States of America)

Website: https://www.fodsupport.org/

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.

MCAD deficiency 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.

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 on MCAD deficiency can be found at: 

• Government of Western Australia Department of Health: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
• Genetic and Rare Diseases (GARD) Information Center: Medium chain acyl-CoA dehydrogenase deficiency
• National Organization for Rare Disorders (NORD): Medium chain acyl-CoA dehydrogenase deficiency 

GeneReviews^®: Medium-chain acyl-coenzyme A dehydrogenase deficiency

Orphanet: Medium chain acyl-CoA dehydrogenase deficiency

Online Mendelian Inheritance in Man (OMIM): #607008 Acyl-CoA dehydrogenase, medium-chain; ACADM 

Human Phenotype Ontology (HPO): Acyl-Coa dehydrogenase, medium-chain, deficiency of 

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

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.