Predicting disease severity in metachromatic leukodystrophy using protein activity and a patient phenotype matrix.

ABSTRACT:

Background

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by mutations in the arylsulfatase A gene (ARSA) and categorized into three subtypes according to age of onset. The functional effect of most ARSA mutants remains unknown; better understanding of the genotype-phenotype relationship is required to support newborn screening (NBS) and guide treatment.

Results

We collected a patient data set from the literature that relates disease severity to ARSA genotype in 489 individuals with MLD. Patient-based data were used to develop a phenotype matrix that predicts MLD phenotype given ARSA alleles in a patient's genotype with 76% accuracy. We then employed a high-throughput enzyme activity assay using mass spectrometry to explore the function of ARSA var

SUBMITTER: Trinidad M 

PROVIDER: S-EPMC10360315 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature