Characterization of late-onset citrullinemia 1 in a Korean patient: confirmation by argininosuccinate synthetase gene mutation analysis

J Biochem Mol Biol. 2006 Jul 31;39(4):400-5. doi: 10.5483/bmbrep.2006.39.4.400.

Abstract

A 16-month old boy was referred to our hospital for evaluation of recurrent generalized tonic clonic seizures. Metabolic evaluation revealed significant hyperammonemia (1,112 microg/dl). Amino acid/acylcarnitine screening using tandem mass spectrometry showed markedly increased plasma levels of citrulline (1,350 microM/l) with undetectable levels of arginine and arginosuccinic acid. Urinary excretion of citrulline was markedly increased (38,617 microM/g creatinine). Brain MRI findings showed diffuse high-signal intensity lesions, that involved gray and white matter in both frontal lobes and insula with edematous changes; these findings were consistent with the acute stage of citrullinemia (CTLN). Mutation analysis of the argininosuccinate synthetase (ASS) gene, in this patient, showed a Gly324Ser mutation in exon 13, and a 67-bp duplication mutation in exon 15 (c.1128-6_1188dup67). The patient was confirmed as having late-onset CTLN1 and treated with anticonvulsants, lactulose enema, protein restricted diet and arginine. Here we describe a case of late-onset CTLN1 in a patient by biochemical analyses and ASS gene mutation confirmation. This is the first report of a Korean patient with late-onset CTLN1 confirmed by ASS gene mutation identification.

Publication types

  • Case Reports

MeSH terms

  • Argininosuccinate Synthase / genetics*
  • Brain / pathology
  • Citrulline / blood
  • Citrulline / urine
  • Citrullinemia / genetics*
  • Citrullinemia / metabolism
  • Citrullinemia / pathology
  • DNA Mutational Analysis
  • Exons
  • Female
  • Gene Duplication
  • Humans
  • Infant
  • Korea
  • Male
  • Mutation, Missense
  • Seizures / genetics
  • Seizures / metabolism

Substances

  • Citrulline
  • Argininosuccinate Synthase