[P1-177] A novel mutation of ARSA gene in one metachromatic leukodystrophy family pedigree
[Objective] Clinical features and enzyme activity of arylsulfatase A (ARSA) in a metachromatic leukodystrophy (MLD) family pedigree with novel mutation was analyzed. [Methods] Proband and related family members’ clinical data were collected. Proband, female, 8 years old, had the manifestations of progressive motor deterioration, language development delay and mental retardation. Sensory integrative functions had moderate disorders. Bilateral brain periventricular white matter demonstrated slightly long T1 and T2 signal with banded signal enhancement on MRI, high signal with strip of equal T1 and T2 signal on fluid-attenuated inversion-recovery sequence(FLAIR) and diffusion-weighted imaging(DWI). Bilateral internal capsule hind legs and corpus callosum showed high signal on DWI. Younger brother of proband was 3 years old, had no obvious symptoms, however, with similar MRI imaging characteristics with his sister. Enzyme activities of arylsulfatase A (ARSA) in leukocyte of proband and her brother were detected. Eight exons of ARSA gene and flanking sequences in peripheral blood of this family pedigree and a hundred normal controls were detected by polymerase chain reaction amplification and Sanger sequencing. [Results] Enzyme activities of ARSA are 2.5nmol/17h/mg Pro and 3.8nmol/17h/mg Pro respectively, much less than normal control. Proband and her brother had same compound heterozygous mutations including p.Arg86Gln heterozygous mutation in exon2 and c.1123-1126delCTCT heterozygous mutation in exon5. Additionally, c.1123-1126delCTCT is a novel mutation. [Conclusion] Enzyme activity defect of ARSA is pathogenesis of MLD. This study analyzed a novel mutation in ARSA gene of a MLD family pedigree, which may result in small amount of residual enzyme activity. We not only explored genotype-phenotype correlations, but also further improved ARSA mutation database.