临床病例报告杂志

Identification of Novel Mutations in Cpt1A Gene in a Patient with Carnitine Palmitoyltransferase IA Deficiency Presenting with Cholestatic Jaundice

Abstract

Saraswathy Apparow, Noornatisha Salleh, Azzah Hana Abu Yamin, Nor Azimah Azize, Ong Fen Ni, Mohd Khairul Nizam Mohd Khalid, Yusnita Yakob and Anasufiza Habib

Background: Carnitine Palmitoyltransferase IA (CPT IA; MIM #255120) deficiency is a rare autosomal recessive inherited disorder of mitochondrial fatty acid oxidation. Patients experience a rapid onset of symptoms which include “Reye-like” hepatic encephalopathy precipitated by fasting or any intercurrent illness, followed by hepatomegaly and hypoketotic hypoglycaemia.

Objective: To perform clinical, biochemical and genetic characterization of a patient with CPT1A deficiency.

Designs and methods: We present a case of a patient with unresolved cholestatic jaundice, failure to thrive and gross developmental delay. Physical examination showed moderate hepatomegaly with mild hypotonia.

Results: Basic laboratory investigations showed moderate transaminitis with cholestasis and compensated metabolic acidosis. Dried blood spot acylcarnitine showed marked elevation of free carnitines (C0) and C0/C16+C18 ratio with suppressed levels of C16, C16OH, C18:1 and C18 Organic acid analysis showed a dicarboxylic aciduria with a prominence of the C12 dicarboxylic (dodecanedioic) acid and increased excretion of 3-methylglutaconic acid. CPT1A mutation analysis identified two novel mutations, c.1244C>A p. (Ala415Glu) in exon 11 and c.1450del p. (Leu484Phefs*47) in exon 12.

Conclusion: Unsuspected CPT1A deficiency was diagnosed in a jaundiced patient from the selective screening for inborn errors and metabolism and confirmed by molecular analysis.