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Metachromatic leucodystrophy in three families from Nova Scotia, Canada: a recurring mutation in the arylsulphatase A
M B Coulter-Mackie1, L Gagnier, M J Beis
1Department of Pediatrics, University of British Columbia, Vancouver, Canada.
Abstract:
Metachromatic leucodystrophy (MLD) is a lysosomal storage disease resulting from a deficiency of arylsulphatase A. We have identified a child with infantile onset MLD who is homozygous for an A212V mutation, a mutation previously reported but not further characterised. We have introduced this mutation into an arylsulphatase A expression vector by site directed mutagenesis. Transient expression of this mutant plasmid in COS cells yields very low levels of arylsulphatase A activity consistent with the patient's phenotype. The arylsulphatase A pseudodeficiency also segregates in this family causing difficulty in interpreting enzyme levels in the absence of DNA data. Two other patients from the same province, also carrying the A212V allele, have juvenile and adult onset MLD and are heterozygous for P426L ("A" allele) and I179S alleles respectively, known late onset alleles.
Insights
Metachromatic leukodystrophy (MLD) is a rare genetic disorder. This study characterizes the A212V mutation in arylsulfatase A, linking it to infantile MLD and aiding diagnosis in affected families.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by arylsulfatase A deficiency.
- Genetic mutations in the arylsulfatase A gene lead to MLD, presenting in infantile, juvenile, or adult forms.