METACHROMATIC LEUKODYSTROPHY IN 3 FAMILIES FROM NOVA-SCOTIA, CANADA -A RECURRING MUTATION IN THE ARYLSULFATASE-A GENE

Metachromatic leucodystrophy (MLD) is a lysosomal storage disease resu lting from a deficiency of arylsulphatase A. We have identified a chil d with infantile onset MLD who is homozygous for an A212V mutation, a mutation previously reported but not further characterised. We have in troduced this mutation into an arylsulphatase A expression vector by s ite directed mutagenesis. Transient expression of this mutant plasmid in COS cells yields very low levels of arylsulphatase A activity consi stent with the patient's phenotype. The arylsulphatase A pseudodeficie ncy 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 all eles respectively, known late onset alleles.