- 作者：Valentina Di Pietro ; Ugo Cavallari ; Angela M. Amorini ; Giacomo Lazzarino ; Salvatore Longo ; Carlo Poggiani ; Pietro Cavalli ; Barbara Tavazzi
- 关键词：Aspartoacylase ; Canavan disease ; HPLC ; Novel missense mutation ; Urinary N-acetylaspartate
- 刊名：Clinical Biochemistry
- 出版年：December, 2013
- 年：2013
- 卷：46
- 期：18
- 页码：1902-1904
- 全文大小：185 K
Objective
Canavan disease (OMIM ) is a severe autosomal recessive neurodegenerative disorder characterized by spongy degeneration of the brain and caused by mutations in the gene encoding for aspartoacylase (ASPA). The enzyme is responsible for the catalyses of the brain-specific compound N-acetylaspartate (NAA).Design and methods
We report the case of two Egyptian sibling patients suspected of Canavan disease (CD) showing clinical deterioration, white matter degeneration, megalencephaly and severe intellectual impairment. The patients underwent magnetic resonance imaging (MRI) and biochemical analysis of NAA in biological fluid samples (serum and urine). Subsequently, in order to determine the mutation responsible for CD in these two sibs, a molecular biological examination was performed.
Results
MRI findings and quantification of high NAA excretion (1378.5 and 680.1 渭mol NAA/mmol creatinine in urine of 4 months and 4 years old patients, respectively) confirmed the diagnosis of CD and prompted a search for the responsible mutation. The molecular biological analysis revealed homozygosity for the substitution T530C (Ile177Thr) in the exon 4 of the ASPA gene in both sibs.
A total loss of enzymatic activity was also recorded.
Conclusions
The substitution T530C (Ile177Thr) results in a novel missense mutation causing a CD phenotype with severe clinical characteristics. This mutation was not previously described in the literature. In these two sibs, urinary concentration of NAA appears to correlate inversely to symptom severity and CD progression.