RESUMO
Canavan disease (CD) is a rare fatal childhood neurological autosomal recessive genetic disease caused by mutations in the ASPA gene, which lead to catalytic deficiency of the ASPA enzyme, which catalyzes the hydrolysis of N-acetyl-L-aspartate (NAA) into aspartate and acetate. CD occurs frequently among Ashkenazi Jewish population, however it has been reported in many other ethnic groups with significantly lower frequency. Here, we report on two Egyptian patients diagnosed with CD, the first patient harbors five missense mutations (c.427 A > G; p. I143V, c.502C > T; p. R168C, c.530 T > C; p. I177T, c.557 T > C; p. V186D c.548C > T; p. P183L) and a silent mutation (c.693 C > T; p. Y231Y). The second patient was found to be homozygous for two missense mutations (c.427 A > G; p. I143V and c.557 T > A; p. V186D). Furthermore, molecular modeling of the novel mutation p. P183L provides an instructive explanation of the mutational impact on the protein structure that can affect the function of the ASPA. Here, the clinical, radiological, and biochemical profile of the two patients are reviewed in details.
