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DOI: 10.1055/s-2005-865865
Georg Thieme Verlag KG Stuttgart · New York
Possible Genotype-Phenotype Correlations in Children with Mild Clinical Course of Canavan Disease
Publication History
Received: February 2, 2005
Accepted after Revision: May 26, 2005
Publication Date:
11 August 2005 (online)
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Abstract
Canavan disease is characterised as a rare, neurodegenerative disease that usually causes death in early childhood. It is an autosomal recessive disorder due to an aspartoacylase (ASPA) deficiency. The causative gene has been mapped to chromosome 17 pter-p13. Here we describe three affected children from two Greek families with an unusually mild course of Canavan disease. All children presented with muscular hypotonia and macrocephaly. Diagnosis was based on elevated N-acetylaspartate in urine, reduced aspartoacylase activity in fibroblasts, and marked white matter changes on cerebral imaging. All three affected individuals exhibited continuous psychomotor development without any regression. Genetic analyses revealed compound heterozygous mutations (Y288 C; F295 S) in two individuals. The Y288 C variant was previously described in a child with macrocephaly, mild developmental delay, increased signal intensity in the basal ganglia, partial cortical blindness and retinitis pigmentosa, and slightly elevated N-acetylaspartate in the urine. Demonstration of the same variant in two unusually mildly affected Canavan disease patients and absence of this variant in 154 control chromosomes suggest a possible pathogenic role in mild Canavan disease. In the third individual, two homozygous sequence variants were identified, which comprise the known G274R mutation and a novel K213E variant.
Key words
Mild Canavan disease - aspartoacylase - ASPA - leukodystrophy
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M.D. Heymut Omran
Department for Paediatric Neurology and Muscle Disorders
University Hospital
Mathildenstraße 1
79106 Freiburg
Germany
Email: omran@kikli.ukl.uni-freiburg.de