Mild elevation of N-acetylaspartic acid and macrocephaly: Diagnostic problem

Sankar Surendran, Fiona J. Bamforth, Alicia Chan, Stephen K. Tyring, Stephen I. Goodman, Reuben Matalon

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Patients with slightly increased excretion of N-acetylaspartic acid in urine, together with macrocephaly, present a dignostic dilemma for Canavan's disease. We describe a 13-year-old male patient with macrocephaly, mild developmental delay, increased signal intensity in the basal ganglia bilaterally, partial cortical blindness, and retinitis pigmentosa. Although the clinical course and magnetic resonance imaging findings did not resemble typical Canavan's disease, N-acetylaspartic acid excretion in the patient's urine was slightly elevated, 99.90 ± 4.00 μg/mg creatinine, whereas the normal control range was < 83 μg/mg creatinine. Cultured skin fibroblasts from the patient showed no aspartoacylase activity. Cloning of genomic DNA isolated from the patient's fibroblasts showed an intronic mutation, specifically deletion of -2A and -3C at the acceptor site of exon 3 and disrupting the normal splicing of the gene. A second mutation was found in exon 6, 863 A→G in aspartoacylase complementary DNA, causing a tyrosine-to-cysteine (Y288C) amino acid substitution. Expression of the mutation on exon 6 showed normal aspartoacylase activity. These data suggest that expression of the mutation may help to understand the enzyme defect in patient with slightly increased N-acetylaspartic acid excretion.

Original languageEnglish (US)
Pages (from-to)809-812
Number of pages4
JournalJournal of Child Neurology
Issue number11
StatePublished - Nov 2003
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology


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