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Updated: May 8, 2026

An In Vitro Model for the Study of Cellular Pathophysiology in Globoid Cell Leukodystrophy
07:45

An In Vitro Model for the Study of Cellular Pathophysiology in Globoid Cell Leukodystrophy

Published on: October 21, 2014

Sixteen novel mutations in the arylsulfatase A gene causing metachromatic leukodystrophy

Paola Luzi1, Mohammad A Rafi, Han Zhi Rao

  • 1Lysosomal Diseases Testing Laboratory, Department of Neurology, Thomas Jefferson University, 1020 Locust Street, Room 346, Philadelphia, PA 19107, USA.

Gene
|September 5, 2013
PubMed

Insights

Researchers identified sixteen novel mutations in the arylsulfatase A (ARSA) gene in patients with metachromatic leukodystrophy (MLD). This expands the known genetic variations contributing to this rare lysosomal storage disorder.

Area of Science:

  • Genetics
  • Biochemistry
  • Rare Diseases

Background:

  • Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disorder.
  • MLD is primarily caused by mutations in the arylsulfatase A (ARSA) gene.

Purpose of the Study:

  • To identify and characterize novel mutations in the ARSA gene in patients diagnosed with MLD.
  • To expand the understanding of the genetic basis of MLD.

Main Methods:

  • Genetic analysis of the ARSA gene in fifteen unrelated MLD patients.
  • Identification and classification of novel and previously reported mutations.

Main Results:

  • Sixteen novel mutations were identified: nine missense, three nonsense, three frameshift, and one splice-site mutation.
  • Three previously reported mutations were found in different allelic contexts, including associations with pseudodeficiency alleles.

Conclusions:

  • The study expands the spectrum of known ARSA gene mutations associated with MLD.
  • Characterizing these novel mutations is crucial for accurate genetic diagnosis and understanding MLD pathogenesis.
Keywords:
ARSAArylsulfatase ADDGenotype–phenotype correlationsLILysosomal storage diseasesMLDMRIMetachromatic leukodystrophyPCRPdSulfatidesWMarylsulfatase Adevelopmental delaylate infantilemagnetic resonance imagingmetachromatic leukodystrophypolymerase chain reactionpseudodeficiencywhite matter

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