Journal of Clinical Case Reports

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.

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