Carnitine uptake deficiency, also known as systemic primary carnitine deficiency, is a genetic metabolic condition that affects the body’s ability to use certain fats called long-chain fatty acids to produce energy.^1-4 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).^3-4

In carnitine uptake deficiency, the OCTN2 carnitine transporter, which helps move carnitine from the blood into cells, does not work properly.¹ This results in low carnitine levels in cells. Without enough carnitine in cells, fatty acids cannot be transported into the mitochondria to be converted to energy. This leads to insufficient energy production, especially during times of increased energy needs such as fasting or illness, and may also cause fats to build up in the liver, muscles, and heart.^1,4 If untreated, this can cause a wide range of symptoms and complications, including the risk of sudden death.^1-3 There may also be individuals with no symptoms (asymptomatic).

In Australia, carnitine uptake 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, carnitine uptake deficiency is often diagnosed after symptoms develop. Early detection and management of carnitine uptake deficiency may help prevent or reduce the risk of life-threatening complications.^2,4

Synonyms:^1-3 Systemic primary carnitine deficiency (SPCD); CDSP; Carnitine transporter defect (CTD); Carnitine uptake deficiency (CUD); Deficiency of plasma-membrane carnitine transporter; Renal carnitine transport defect

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:158 Systemic primary carnitine deficiency

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

Symptoms of carnitine uptake deficiency varies widely between individuals, and can differ in terms of severity of symptoms, age of onset (age when the symptoms present) and the body organs that are involved.² Below are some of the symptoms that may develop if the condition is untreated; this may not cover all the symptoms of untreated carnitine uptake deficiency:

Symptoms may develop in early childhood, usually within the first few months or 2 years of life.^1,2,4 Babies may have episodes of hypoketotic hypoglycaemia (low blood glucose and low or absence of ketone bodies) which can be brought upon by fasting or illnesses. Babies may show extreme tiredness and lack of energy (lethargy), irritability and have poor feeding. They may also have an enlarged liver (hepatomegaly). If the hypoketotic hypoglycaemia is not treated promptly, this can lead to seizures, coma and early death.² Repeated episodes may lead to long term complications such as decreased muscle tone, dystonia (movement disorder) and others. Children may also go on to develop heart issues like cardiomyopathy (where the heart has difficulty pumping blood to the rest of the body).

For some children, the symptoms mainly affect the heart and muscles and often present between the age of two to four years old.^1,2 Symptoms include weak muscle tone (hypotonia), skeletal muscle weakness, and heart issues such as cardiomyopathy, which can progress (worsen) to heart failure and death.^1,2,4

In some cases, symptoms may not present until adulthood. A common symptom in adulthood is fatigue (extreme tiredness).^1,2,4 Some people may have heart complications, such as cardiac arrhythmias (irregular heartbeats).^1,2 There are reported cases of sudden death.^1,2,6 For others, there may be no symptoms at all (asymptomatic). Some symptoms, such as cardiac arrhythmias, can develop or worsen during pregnancy.^1,2

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.

Orphanet: Disability – Systemic primary carnitine deficiency has information about the  activity limitations that people with carnitine uptake deficiency may face; please note that this was last updated in 2022 and may not reflect the most current information.

Carnitine uptake deficiency is a genetic condition. It is caused by disease-causing genetic changes (variants) in the SLC22A5 gene on chromosome 5.^1,5 The SLC22A5 gene is responsible for producing the OCTN2 protein that is involved in transport of carnitine in cells. The carnitine attaches to fatty acids and helps transport the fatty acids into the mitochondria where fatty acids are used to produce energy.

All individuals have two copies (alleles) of the SLC22A5 gene – one copy inherited from each parent. Carnitine uptake deficiency is an autosomal recessive condition, which means both copies of the SLC22A5 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, carnitine uptake 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 carnitine uptake 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 carnitine uptake 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, carnitine uptake deficiency is often diagnosed after symptoms develop.

Diagnosis of carnitine uptake deficiency may be made based on clinical evaluation of symptoms, laboratory tests on blood samples to detect for low levels of carnitine, and confirmed by genetic testing and/or reduced enzyme activity measured in skin fibroblast cells.^1,6

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 organic acidemias, fatty acid oxidation defects, isovaleric acidemia and propionic acidemia.^1,2,4

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 carnitine uptake deficiency. Early diagnosis and appropriate management can help prevent or reduce development of symptoms and the risk of life-threatening complications, including risk of sudden death.^2,6

Management of carnitine uptake deficiency involves life-long oral carnitine supplementation to prevent carnitine deficiency, and measures to prevent hypoglycaemia and to reduce risk to metabolic, hepatic (liver), cardiac (heart), & muscular complications.^2,4  The dose of carnitine may differ between individuals. Carnitine concentrations in the blood should be monitored regularly and the dose may need to be adjusted accordingly.² Frequent meals and avoidance of fasting is required to avoid hypoglycaemia.^2,4 Additional measures may need to be taken during time of illness and in circumstances where fasting is required (such as before surgical procedures) – this may involve adjusting the carnitine dose, carbohydrate supplementation or provision of high calorie or high energy fluids.² Pregnant women are also recommended to have their carnitine concentration closely monitored, even if they previously have not had any symptoms (asymptomatic), as pregnancy may bring upon or worsen the symptoms.²

In addition to regular monitoring of carnitine concentrations in the blood, cardiac (heart) evaluations are also recommended.²

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 carnitine uptake deficiency may include general practitioners (GP), paediatricians, geneticists, metabolic physicians, genetic counsellors, cardiologists, 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 be managed by a metabolic specialist team.²

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 carnitine uptake deficiency, including when presenting to emergency departments:²

• people with carnitine uptake deficiency are at risk of hypoglycaemia and metabolic, hepatic, cardiac, & muscular complications, particularly if they don’t have frequent feeds or are without food for periods of time (fasting should be avoided)
• Intravenous (IV) glucose is recommended for those who have to fast due to medical or surgical procedures or who cannot tolerate oral intake due to illness (such as gastroenteritis); a metabolic specialist team should be consulted

GeneReviews^®:Primary Carnitine Deficiency (Management section) includes recommendations for emergency outpatient treatment and acute inpatient treatment.

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 uptake 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 uptake deficiency can be found at: 

• Genetic and Rare Diseases (GARD) Information Center: Systemic primary carnitine deficiency disease
• National Organization for Rare Disorders (NORD): Systemic Primary Carnitine Deficiency

Orphanet: Systemic primary carnitine deficiency

Online Mendelian Inheritance in Man (OMIM^®): #212140 – Carnitine deficiency, systemic primary; CDSP

GeneReviews^®: Primary Carnitine 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.