title: Mild elevation of N-acetylaspartic acid and macrocephaly: diagnostic problem.
abstract: 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 microg/mg creatinine, whereas the normal control range was < 83 microg/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 a patient with slightly increased N-acetylaspartic acid excretion.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas 77555-0359, USA.
authors.forename: Sankar
authors.initials: S
authors.lastname: Surendran
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Bamforth
authors.forename: Alicia
authors.initials: A
authors.lastname: Chan
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Tyring
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Goodman
authors.forename: Reuben
authors.initials: R
authors.lastname: Matalon
mesh_terms: D000293:Adolescent; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000652:urine*; D001921:Brain / Q000002:abnormalities*; D017825:Canavan Disease / Q000175:diagnosis* / Q000235:genetics / Q000652:urine*; D006801:Humans; D008297:Male
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate