HIGH RESIDUAL ARYLSULFATASE-A (ARSA) ACTIVITY IN A PATIENT WITH LATE-INFANTILE METACHROMATIC LEUKODYSTROPHY

We identified a patient suffering from late-infantile metachromatic le ukodystrophy (MLD) who has a residual arylsulfatase A (ARSA) activity of about 10%. Fibroblasts of the patient show significant sulfatide de gradation activity exceeding that of adult MLD patients. Analysis of t he ARSA gene in this patient revealed heterozygosity for two new mutan t alleles: in one allele, deletion of C 447 in exon 2 leads to a frame shift and to a premature stop codon at amino acid position 105; in the second allele, a G-->A transition in exon 5 causes a Gly309-->Ser sub stitution. Transient expression of the mutant Ser309-ARSA resulted in only 13% enzyme activity of that observed in cells expressing normal A RSA. The mutant ARSA is correctly targeted to the lysosomes but is uns table. These findings are in contrast to previous results showing that the late-infantile type of MLD is always associated with the complete absence of ARSA activity. The expression of the mutant ARSA protein m ay be influenced by particular features of oligodendrocytes, such that the level of mutant enzyme is lower in these cells than in others.