Carnitine palmitoyltransferase II (CPT II) 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 These long-chain fatty acids 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). Once in the mitochondria, the CPT II enzyme converts the acylcarnitine (fatty acid + carnitine) back into acyl-CoA. This allows a process called β-oxidation to take place and produce energy.^2,3 In CPT II deficiency, the CPT II enzyme does not work properly, which prevents or reduces the conversion of acylcarnitine to acyl-CoA. This results in the body being unable to produce enough energy, especially during times of fasting or exercise and accumulation of long-chain acylcarnitines, which can be toxic to muscles, heart and liver.

Three forms of CPT II deficiency have been described:^1-7

• myopathic form – affects mainly muscles during times of stress such as exercise
• severe infantile hepatocardiomuscular form – usually presents within the first two years of life; affects multiple organ systems and can lead to life-threatening complications, including early death
• lethal neonatal form – very severe form and results in early death; has symptoms of infantile form as well as some physical abnormalities (dysmorphic) such as cystic dysplastic kidneys (where there is abnormal kidney development)

In Australia, CPT II deficiency is often detected shortly after birth via newborn bloodspot screening (NBS) programs. Additional testing is required to confirm the diagnosis. For individuals who are not screened at birth, CPT II deficiency is often diagnosed after symptoms develop.

Synonyms:¹ CPT2; CPTII; Carnitine palmitoyltransferase deficiency type 2

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:157 Carnitine palmitoyltransferase II deficiency

ICD-11: 5C52.00 Disorders of carnitine transport or the carnitine cycle

Symptoms of CPT II deficiency varies between individuals. The symptoms of CPT II deficiency are often described as three main forms:

Myopathic

This form of CPT II deficiency mainly affects the muscles. Symptoms often present during childhood, but in some cases it can present in the teenage years or in adulthood.² Symptoms may include myalgia (muscle pain), muscle weakness, muscle cramps and myoglobinuria (presence of a muscle protein called myoglobin in the urine, which is caused by muscle breakdown known as rhabdomyolysis).^1-5 Episodes of the symptoms are usually brought upon (triggered) by exercise, infections, fasting or extreme changes in temperature. For some individuals, they may not have any symptoms between the episodes (asymptomatic), whilst others may have some muscle pain affecting daily activities.²

Severe infantile hepatocardiomuscular form

Symptoms usually present within the first two years of life and may include:^2,6

• hypoketotic hypoglycemia – a type of metabolic crisis in which the body develops low blood sugar and low ketone levels because it cannot properly use stored fat for energy); this can lead to sudden death if untreated
• liver complications including hepatomegaly (enlarged liver), episodic hyperammonaemia (toxic build up of ammonia in blood that can affect brain function) and liver failure
• heart issues such as ventricular arrhythmias (abnormal heart rhythms that start from ventricles, which are lower chambers of the heart) and cardiomyopathy (disease of the heart muscle that makes it harder for the heart to pump blood). These complications can lead to sudden death if untreated.
• myopathy (muscle disease causing muscle weakness)

Lethal neonatal form

Symptoms present within days after birth and include respiratory distress (difficulty breathing) and hypoketotic hypoglycemia. There are also liver and heart complications similar to the infantile form, as well as dysmorphic features (physical abnormalities) such as cystic dysplastic kidneys (where there is abnormal kidney development) that can lead to kidney disease and failure.^1,2 This form of CPTII deficiency usually leads to early death often within days or a few months,^2,7 especially if untreated.

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.

CPT II deficiency is a genetic condition. It is caused by disease-causing genetic changes (variants) in the CPT2 gene on chromosome 1.² The CPT2 gene provides instructions to make the the CPT II enzyme. The CPT II enzyme is responsible for converting acylcarnitine (fatty acid + carnitine) back into acyl-CoA, which are then ready to enter the β-oxidation pathway to produce energy.³

All individuals have two copies (alleles) of the CPT2 gene – one copy inherited from each parent. CPT II deficiency is an autosomal recessive condition, which means both copies of the CPT2 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, CPT II 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 CPT II deficiency. If the test results suggest that there is a risk of the baby having one of 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 CPT II 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, CPT II deficiency is often diagnosed after symptoms develop.

Diagnosis of CPT II deficiency may be made based on clinical evaluation of symptoms, laboratory tests on blood samples to detect for increased levels of particular acylcarnitines, and confirmed by measurement of CPT II enzyme activity in muscle or fibroblast (skin) cells or genetic testing.^1,2

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 McArdle disease, Duchenne muscular dystrophy, and cytochrome c oxidase deficiency (differential diagnosis for myopathic form) or  carnitine-acylcarnitine translocase deficiency (CACT) and very-long-chain acyl-CoA dehydrogenase deficiency (differential diagnosis for the infantile and neonatal forms).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 CPT II deficiency . Treatment of CPT II deficiency is mainly focussed on avoiding prolonged periods of fasting (people with CPT II deficiency need to be eating regularly and not go without food for long periods of time such as more than 12 hours) and they need to be on a low-fat, high-carbohydrate diet.^1,2 Treatment may also involve medium-chain triglyceride supplementation.^2,3 Carnitine supplementation may be considered in some cases but may not always be used; its use is said to be controversial as it may be a risk factor for cardiac arrhythmias (irregular heartbeats) in long chain fatty acid oxidation disorders.²

Hypoketotic hypoglycemia and hepatic encephalopathy (a condition in which toxins build up in the blood because the liver is not able to remove them effectively, resulting in impaired brain function) are medical emergencies and should be treated promptly and accordingly.²

People with CPT II deficiency also need to be treated accordingly for liver damage, heart complications, rhabdomyolysis and myoglobinuria.

Early diagnosis and treatment can help reduce metabolic crises and risk of serious complications including sudden death. For the neonatal form of CPT II deficiency, early death may still occur despite treatment. There are reports of babies with the infantile or neonatal-onset of CPT II deficiency who received early and intensive treatment and have survived into childhood..^8,9

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 CPT II deficiency may include general practitioners (GP), paediatricians, geneticists, metabolic physicians, genetic counsellors, neurologists, hepatologists, gastroenterologists, cardiologists, nephrologists, and other healthcare professionals trained to look after metabolic disorders. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here. 

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 CPT II deficiency, including when presenting to emergency departments:²

• extended fasting and prolonged exercise are to be avoided
• general anaesthesia should be done with caution as there may be a risk of malignant hyperthermia or rhabdomyolysis
• people with CPT I deficiency are at risk of hypoketotic hypoglycaemia and hepatic encephalopathy, particularly during fasting, illness, or other metabolic stress. These are medical emergencies that require immediate treatment. 
• metabolic specialist team should be consulted

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries. For more information, please visit the RARE Portal’s Considerations for Participating in Health and Medical Research page.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in research, including clinical trials,  with your medical team to determine suitability and eligibility.

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.

Carnitine palmitoyltransferase II 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 carnitine palmitoyltransferase II deficiency can be found at: 

• Genetic and Rare Diseases (GARD) Information Center: Carnitine palmitoyltransferase ii deficiency

Orphanet: Carnitine palmitoyltransferase II deficiency

GeneReviews^®: Carnitine Palmitoyltransferase II Deficiency

Online Mendelian Inheritance in Man (OMIM^®): #600649 – Carnitine palmitoyltransferase II deficiency, Infantile

Online Mendelian Inheritance in Man (OMIM^®):#255110 – Carnitine palmitoyltransferase II deficiency, myopathic, stress-induced

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.