Carnitine palmitoyl transferase 1A deficiency

Carnitine palmitoyl transferase 1A (CPT1A) deficiency, also known as CPT1 deficiency or hepatic carnitine palmitoyltransferase I deficiency, is a rare inherited disorder of long-chain fatty acid oxidation. The condition is caused by mutations in the CPT1A gene, which encodes the liver isoform of carnitine palmitoyltransferase 1, an enzyme located on the outer mitochondrial membrane. This enzyme is essential for transporting long-chain fatty acids into the mitochondria, where they are broken down (beta-oxidation) to produce energy, particularly during periods of fasting or physiological stress. CPT1A deficiency primarily affects the liver, brain, and kidneys. During episodes of metabolic crisis — typically triggered by fasting, illness, or prolonged exercise — the body cannot adequately use long-chain fatty acids for energy. This leads to hypoketotic hypoglycemia (low blood sugar with inappropriately low ketone production), which can cause seizures, loss of consciousness, and potentially life-threatening hepatic encephalopathy. Characteristic laboratory findings include elevated free carnitine levels in the blood, low acylcarnitine levels, and hepatomegaly with elevated liver transaminases during acute episodes. Renal tubular acidosis has also been reported in some patients. Management of CPT1A deficiency focuses on prevention of metabolic crises through avoidance of prolonged fasting, maintaining a diet low in long-chain fats and supplemented with medium-chain triglycerides (MCT), and ensuring adequate carbohydrate intake, especially during illness. Emergency protocols with intravenous glucose are critical during acute decompensation. With early diagnosis — increasingly identified through newborn screening programs — and careful dietary management, many patients can have a favorable long-term outcome. However, episodes of metabolic decompensation can be fatal if not promptly treated. A high prevalence of a specific CPT1A variant (c.1436C>T, p.P479L) has been identified in certain Arctic Indigenous populations, including Inuit and Alaska Native communities, though the clinical significance of this variant remains a subject of ongoing research.

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