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Updated: Apr 8, 2026
An In Vitro Model for the Study of Cellular Pathophysiology in Globoid Cell Leukodystrophy
Published on: October 21, 2014
Biochemical and Genetic Analysis of Seven Korean Individuals With Suspected Metachromatic Leukodystrophy
Minje Han1, Sun-Hee Jun2, Yun-Jin Lee3
1Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
Abstract:
Metachromatic leukodystrophy (MLD) is an autosomal recessive disease caused by a deficiency in arylsulfatase A (ARSA). However, decreased ARSA activity is also observed in pseudodeficiency (PD). To distinguish between MLD and PD, we performed gene mutation and sulfatide analyses by using dried blood spots (DBSs) from seven Korean individuals who underwent an analysis of ARSA activity. DNA was extracted from DBSs, and PCR-direct sequencing of ARSA was performed. The cDNA obtained was analyzed to confirm a novel mutation. Of the seven subjects, three were confirmed as having MLD, one was confirmed as having MLD-PD, one was confirmed as having PD, and the remaining two were obligate heterozygotes. We verified the novel pathogenic variant c.1107+1delG by performing familial and cDNA analyses. Sulfatide concentrations in DBSs were analyzed and were quantified by using ultra-performance liquid chromatography and tandem mass spectrometry, respectively. Total sulfatide concentration was inversely correlated with ARSA activity (Spearman's coefficient of rank correlation, P=0.929, P=0.0025). The results of this mutational and biochemical study on MLD will increase our understanding of the genetic characteristics of MLD in Koreans.
Insights
Metachromatic leukodystrophy (MLD) diagnosis is improved by distinguishing it from pseudodeficiency (PD) using gene and sulfatide analysis. This study identified a novel mutation, aiding genetic characterization in Korean populations.
Area of Science:
- Genetics
- Biochemistry
- Rare Diseases
Background:
- Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder.
- Deficiency in arylsulfatase A (ARSA) causes MLD, but reduced ARSA activity also occurs in pseudodeficiency (PD).
- Distinguishing MLD from PD is crucial for accurate diagnosis and management.
Observation:
- This study analyzed seven Korean individuals with decreased ARSA activity using dried blood spots (DBSs).
- Methods included ARSA gene mutation analysis via PCR-direct sequencing and sulfatide quantification.
- A novel pathogenic variant, c.1107+1delG, was identified and verified.
Findings:
- Three subjects were diagnosed with MLD, one with MLD-PD, one with PD, and two were identified as obligate heterozygotes.
- Sulfatide concentrations in DBSs showed an inverse correlation with ARSA activity.
- The novel variant c.1107+1delG was confirmed through familial and cDNA analyses.
Implications:
- This research enhances the understanding of MLD's genetic landscape in the Korean population.
- The combined gene mutation and sulfatide analysis approach provides a robust method for differentiating MLD from PD.
- These findings contribute to improved diagnostic strategies for MLD and related disorders.
