Carnitine palmitoyltransferase 1A deficiency (CPT1A)
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An infant of Inuit ancestry presents with hypoketotic hypoglycemia, hepatomegaly, and elevated transaminases after a viral illness. Newborn screening flagged a very high C0 (free carnitine) with low long-chain acylcarnitines.
AR; CPT1A (liver/kidney isoform on the outer mitochondrial membrane). A founder variant (c.1436C>T, p.Pro479Leu) is highly prevalent in Inuit, Yup'ik, and Hutterite populations.
CPT1B (muscle isoform) and CPT1C (brain) are not associated with classical disease in humans.
- Hepatic-only phenotype: hypoketotic hypoglycemia, hepatomegaly, transaminitis during fasting or illness
- No cardiomyopathy and no skeletal myopathy (the muscle isoform is intact)
- Renal tubular acidosis can occur
- On RUSP
- Newborn screening (RUSP) acylcarnitine profile: high free carnitine (C0) with low long-chain acylcarnitines, giving an elevated C0/(C16+C18) ratio (the signature, opposite of carnitine uptake defect)
- Reduced CPT1 enzyme activity in cultured fibroblasts
- Confirmatory CPT1A molecular testing (the Inuit/Yup'ik/Hutterite founder variant c.1436C>T, p.Pro479Leu)
- Avoid fasting; emergency IV dextrose during illness
- MCT-rich diet is well tolerated (medium-chain fats bypass CPT1)
NBS: high C0, low long-chain acylcarnitines. The opposite of carnitine uptake defect (which has low C0). CPT1 sits at the entrance to the mitochondrion; when it fails, free carnitine piles up outside while long-chain acylcarnitines cannot form. High C0/(C16+C18) ratio is the diagnostic signature.
"1 is for the liver": CPT1A is the liver isoform, so the phenotype is liver-dominant (hepatomegaly, hypoglycemia) without the cardiac or muscle involvement seen in CPT2 or CACT.