Carnitine acylcarnitine translocase (CACT) deficiency is a genetic, metabolic condition that affects the body’s ability to use certain fats called long-chain fatty acids to produce energy.^1,2 These fats are normally transported into the mitochondria (the part of cells that make energy), with the help of a molecule called carnitine (which the body obtains from food). Carnitine attaches to the fatty acids to form long-chain acylcarnitines, which are then transported into the mitochondria to be broken down to produce energy.^3,4

In CACT deficiency, a protein called carnitine acylcarnitine translocase, which acts as the transporter for these long-chain acylcarnitines, does not function properly. As a result, the long-chain fatty acids cannot enter the mitochondria efficiently, resulting in not enough energy being produced, especially during fasting or illness.¹ There is also a build-up of the long-chain acylcarnitines in the body that can be toxic. This can lead to low blood sugar (hypoglycaemia), metabolic crises, and other severe symptoms and complications.^1-4

In Australia, CACT deficiency is often detected shortly after birth via newborn bloodspot screening (NBS) programs. Additional testing is required to confirm a diagnosis. For individuals who are not screened at birth, CACT deficiency is often diagnosed after symptoms develop. Early detection and management of CACT deficiency is important to prevent life-threatening symptoms.³

Synonyms:^4,5 CACT deficiency; CACTD

CACT deficiency may have previously been referred to as CATR deficiency and carnitine-acylcarnitine carrier (CAC) deficiency.³

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:159 Carnitine-acylcarnitine translocase deficiency

ICD11: 5C52.00 Disorders of carnitine transport or the carnitine cycle

Symptoms of CACT deficiency may vary widely between individuals in severity.^1,3 

In many cases, the symptoms are severe and life-threatening resulting in sudden and early death.³ This may be known as severe neonatal onset disease or  severe classical-onset CACT deficiency. ^3,5 The symptoms present within the first 48 hours after birth as metabolic crisis.^3,4 Newborns may have hypoketotic hypoglycaemia (low ketone and blood sugar levels) and hyperammonaemia (toxic build up of ammonia in blood that can affect brain function) and may show symptoms such as poor feeding, lethargy (extreme tiredness and lack of energy), low muscle tone (hypotonia), muscle weakness and seizures.^1-4 They may also have cardiac arrhythmias (abnormal heart rhythms), cardiomyopathy (disease of the heart muscle that makes it harder for the heart to pump blood), rhabdomyolysis (breakdown of muscle) an enlarged liver (hepatomegaly) and other liver issues. Repeated episodes of hypoketotic hypoglycaemia and hyperammonaemia may lead to developmental delay and intellectual disability if left untreated. Timely treatment of the severe form of CACT deficiency may reduce the risk of early death and lead to better outcomes for some individuals.^3,4

There are also milder (attenuated) forms of CACT deficiency, where symptoms will present later (this could be within the first few months of life or sometime in early childhood) and are often less severe.^1-4 Individuals may still have episodes of metabolic crisis with hypoketotic hypoglycaemia and hyperammonemia, particularly during times of illness or fasting, but less frequently.^1,3  The milder form of CACT deficiency can be managed well with early diagnosis and treatment.^1,4

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.

CACT deficiency is a genetic condition. It is caused by disease-causing genetic changes (variants) in the SLC25A20 gene on chromosome 3.^3,4 The SLC25A20 gene is responsible for producing an enzyme called carnitine-acylcarnitine translocase (CACT) that is involved in transport of long-chain acylcarnitines into the mitochondria where fatty acid oxidation occurs.

All individuals have two copies (alleles) of the SLC25A20 gene – one copy inherited from each parent. CACT deficiency is an autosomal recessive condition, which means both copies of the SLC25A20 gene must have the disease-causing genetic variants.^3,4 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, CACT 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 CACT 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 CACT 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, CACT deficiency is often diagnosed after symptoms develop.

Diagnosis of CACT deficiency may be made based on clinical evaluation of symptoms, laboratory tests on blood samples to detect for increased levels of specific acylcarnitines, and confirmed by genetic testing or in rare cases, analyses of enzyme activity.^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 the neonatal and severe infantile forms of carnitine palmitoyl transferase II (CPT II) deficiency, carnitine transporter deficiency (CT), Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD), TANGO2-related metabolic encephalopathy and arrhythmias, and mitochondrial trifunctional protein deficiency (MTP).¹

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 CACT deficiency. Treatment of CACT deficiency is mainly aimed at avoidance of fasting (not going without food for a period of time) and being on a low-fat, high carbohydrate diet.^3,4 This may also involve continuous overnight feeding (in younger children) and use of uncooked cornstarch as a source of complex carbohydrates at bedtime to ensure there is sufficient glucose supply during the night (for older individuals or those that are less severely affected).³  The recommended maximum time between food may depend on severity of the condition and age.  There may also be medium-chain triglyceride supplementation and carnitine supplementation.

Hypoketotic hypoglycaemia and hyperammonaemia are medical emergencies and should be treated promptly and accordingly. People with CACT deficiency also need to be monitored and treated accordingly for heart complications, rhabdomyolysis and kidney issues.^1,3

Management of symptoms may also include tube feeding, physiotherapy and occupational therapy.³

Early diagnosis and timely treatment of CACT deficiency can help lead to better overall outcomes for individuals. For the severe form, early death may still occur despite treatment, but there are also reports of individuals in their late childhood or early adulthood.^3,5 As for the milder form of CACT deficiency, it can be managed well with early diagnosis and treatment.

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 CACT deficiency may include general practitioners (GP), paediatricians, geneticists, metabolic physicians, genetic counsellors, metabolic dietitians, cardiologists, neurologists, physiotherapists, occupational therapists, speech therapists and other healthcare professionals trained to look after metabolic conditions. 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.³

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.

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 CACT deficiency, including when presenting to emergency departments:³

• prolonged fasting should be avoided
• individuals at risk of hypoketotic hypoglycaemia and hyperammonaemia, particularly if they don’t have frequent feeds or are without food for periods of time. These are medical emergencies that require immediate treatment.
• individuals should be monitored for metabolic, hepatic, cardiac, muscular and renal complications
• there is recommendation that prolonged use of anaesthetics that contain high doses of long-chain fatty acids, such as propofol, avoided
• metabolic specialist team should be consulted

The following organisation provides support for all mitochondrial conditions.

Australian Organisation:

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

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.

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.

CACT 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 CACT deficiency can be found at: 

• Genetic and Rare Diseases (GARD) Information Center: Carnitine-acylcarnitine translocase deficiency
• National Organization for Rare Disorders (NORD): Carnitine-Acylcarnitine Translocase Deficiency

Orphanet: Carnitine-acylcarnitine translocase deficiency

GeneReviews^®:Carnitine-Acylcarnitine Translocase Deficiency

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.