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 a patient with slightly increased N-acetylaspartic acid excretion. (J Child Neurol 2003;18:809—812).

Journal of Inherited Metabolic DiseaseVolume 17, Issue 3 p. 330-332 Short Communication Structural anomalies in patients with inherited metabolic diseases F. J. Bamforth, F. J. Bamforth Departments of Laboratory Medicine and Pathology, and Pediatrics, University of Alberta Hospitals, Edmonton, Alberta, T6G 2B7 CanadaSearch for more papers by this authorJ. S. Bamforth, J. S. Bamforth Departments of Laboratory Medicine and Pathology, and Pediatrics, University of Alberta Hospitals, Edmonton, Alberta, T6G 2B7 CanadaSearch for more papers by this authorD. A. Applegarth, D. A. Applegarth Biochemical Diseases Laboratory, British Columbia's Children's Hospital, Vancouver, British Columbia, CanadaSearch for more papers by this author F. J. Bamforth, F. J. Bamforth Departments of Laboratory Medicine and Pathology, and Pediatrics, University of Alberta Hospitals, Edmonton, Alberta, T6G 2B7 CanadaSearch for more papers by this authorJ. S. Bamforth, J. S. Bamforth Departments of Laboratory Medicine and Pathology, and Pediatrics, University of Alberta Hospitals, Edmonton, Alberta, T6G 2B7 CanadaSearch for more papers by this authorD. A. Applegarth, D. A. Applegarth Biochemical Diseases Laboratory, British Columbia's Children's Hospital, Vancouver, British Columbia, CanadaSearch for more papers by this author First published: 01 May 1994 https://doi.org/10.1007/BF00711821Citations: 6AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume17, Issue3May 1994Pages 330-332 RelatedInformation

A girl aged eight months, who presented with developmental delay and dislocated optic lenses, was diagnosed as having combined sulfite oxidase and xanthine dehydrogenase deficiencies consistent with molybdenum cofactor deficiency. The diagnosis was confirmed by demonstrating the absence in urine of urothione, a molybdenum cofactor metabolite. Prenatal diagnosis excluded the disease in the mother's second pregnancy. A summary of an in vitro study of molybdenum cofactor synthesis in the patient is given.