Carnitine deficiency: primary and secondary causes, symptoms and treatment

Carnitine is a natural substance that, as MedlinePlus explains, is acquired mostly through food and used by cells to process fats and produce energy. It carries fatty acids into the mitochondria, the energy-producing parts of cells. During fasting, fatty acids become the most important energy source for the heart and other muscles, so a shortage of carnitine matters most when you have not eaten or are unwell.

GPnotebook, a reference used by UK GPs, describes carnitine deficiency as primary or secondary. Primary carnitine deficiency, also known as carnitine uptake defect or carnitine transporter deficiency, is an autosomal recessive disorder of the carnitine cycle that impairs fatty acid oxidation. Secondary deficiency can be hereditary, for example as a consequence of other metabolic disorders, or acquired.

MedlinePlus says variants in the SLC22A5 gene cause an absent or dysfunctional OCTN2 protein, which transports carnitine into cells, so that cells lack carnitine, fatty acids cannot enter mitochondria to be used for energy and can build up and damage the liver, heart and muscles. GPnotebook adds that the defect also causes urinary carnitine wasting and low blood carnitine levels.

The condition is rare and varies in severity. MedlinePlus gives a frequency of approximately 1 in 100,000 newborns worldwide and 1 in 40,000 in Japan; GPnotebook gives about 1 in 40,000 with a carrier rate of around 1 percent and notes it is reported to be higher in the Faroe Islands. Some people are asymptomatic, but MedlinePlus says all individuals with the disorder are at risk for sudden death, and that the condition can be mistaken for Reye syndrome.

MedlinePlus explains that the parents of an individual with an autosomal recessive condition each carry one copy of the altered gene but typically do not show signs of the condition themselves.

GPnotebook says secondary deficiencies can be caused by organic acidaemias, defects of fatty acid oxidation and defects of the carnitine cycle, and that carnitine deficiency can also be acquired through liver disease, renal disease such as Fanconi syndrome or renal tubular acidosis, premature birth, dietary insufficiency (chronic parenteral nutrition, malabsorption or soy-based infant formula) and drug therapy including valproate and pivmecillinam or pivampicillin.

Low carnitine from these causes is a consequence of another problem, so the aim is to address the underlying condition and, where appropriate, supplement. Do not start carnitine supplements without medical advice. A separate guide on this site covers L-carnitine as a supplement in heart failure.

Symptoms vary with age. GPnotebook says clinical features vary widely but are typically episodes of low blood sugar without ketones, an enlarged liver, raised liver enzymes and raised ammonia in infants; skeletal muscle disease, raised creatine kinase and cardiomyopathy in childhood; and cardiomyopathy, arrhythmias or fatigability in adulthood. MedlinePlus lists, in infancy or early childhood, severe brain dysfunction (encephalopathy), a weakened and enlarged heart, vomiting, muscle weakness and low blood glucose.

MedlinePlus identifies fasting and illnesses such as viral infections as triggers, so a child or adult with a known metabolic condition who becomes unwell during illness or fasting, with symptoms such as repeated vomiting or unusual drowsiness, needs urgent medical assessment through NHS 111 or A&E. For ongoing tiredness, breathlessness or palpitations, contact your GP or specialist team.

Diagnosis rests on measuring carnitine levels in blood and urine and on genetic testing. A published case report describes a boy whose serum free carnitine was extremely low with increased urinary carnitine, indicating primary carnitine deficiency, and whose diagnosis was later confirmed genetically. The NHS newborn blood spot test checks for a defined list of inherited metabolic diseases; the NHS page lists phenylketonuria, MCADD, maple syrup urine disease, isovaleric acidaemia, glutaric aciduria type 1, homocystinuria and hereditary tyrosinaemia type 1, and primary carnitine deficiency is not named among them, so that test would not be expected to detect it.

A specialist metabolic team is usually involved in confirming the diagnosis and planning care.

The published case report states that primary carnitine deficiency is treatable with lifelong carnitine supplementation, and describes a young man whose heart function recovered fully on carnitine, then relapsed with heart failure after he stopped treatment and monitoring, and improved again when carnitine was restarted. The authors highlight the importance of continued monitoring and the risk during the transition from paediatric to adult care.

MedlinePlus notes that problems can be triggered by fasting or infection, so avoiding prolonged fasting and seeking early advice during illness is part of day-to-day management. Your metabolic team will tailor the plan to you.

In the UK, inherited metabolic disorders are diagnosed and managed by NHS specialist metabolic services. Private genetic and metabolic testing exists, but long-term monitoring and treatment are best delivered by a specialist team that sees these rare conditions regularly. No UK patient leaflet dedicated to carnitine deficiency was found while preparing this page, so the main sources are a UK clinician reference, a US National Library of Medicine resource and a published case report.