CPT1A

CPT1A, or carnitine palmitoyltransferase I, is the liver isoform of an enzyme that resides on the outer mitochondrial membrane and catalyzes the first step of long-chain fatty acid oxidation. It transfers the long-chain acyl group from acyl-CoA to carnitine, forming acylcarnitine that is shuttled into the mitochondrial matrix for beta-oxidation. CPT1A activity is a rate-limiting control point in mitochondrial fatty acid oxidation and is inhibited by malonyl-CoA, linking fatty acid synthesis to degradation.

The CPT1A gene encodes the liver-specific isoform of this enzyme. CPT1A is primarily expressed in the liver, with related isoforms in other tissues: CPT1B in muscle and CPT1C in brain. These different isoforms reflect tissue-specific needs for fatty-acid oxidation.

Clinically, CPT1A deficiency is an autosomal recessive disorder of mitochondrial fatty acid oxidation. It typically presents in infancy or early childhood with episodes of hypoketotic hypoglycemia, hepatomegaly, liver dysfunction, vomiting, and, in some cases, seizures or coma, particularly during fasting or intercurrent illness. The condition can be precipitated by prolonged fasting or infections and may lead to metabolic crisis if not managed. Some individuals carry variants with milder or variable symptoms.

Diagnosis is established by genetic testing of the CPT1A gene, with supportive biochemical clues from acylcarnitine profiles and other metabolic tests; newborn screening may detect abnormalities in some cases. Management emphasizes avoidance of prolonged fasting, rapid carbohydrate administration during illness, and dietary modification to reduce long-chain fat intake while using medium-chain triglycerides, which bypass CPT1A for mitochondrial entry. Prognosis improves with early recognition and appropriate management. Epidemiologically, a common founder variant, CPT1A P479L, occurs in some Arctic populations, particularly among Inuit and Alaska Native groups, with variable clinical significance.