Metachromatic Leukodystrophy (MLD) and
Multiple Sulfatase Deficiency (MSD) are rare and ultra-rare
lysosomal storage diseases. Due to
enzyme defects, patients are unable to split the sulfategroup from the respective substrates. In MSD all
sulfatases are affected due to a defect of the
Sulfatase Modifying Factor 1 (SUMF1) gene coding for the
formylglycine generating
enzyme (FGE) necessary for the modification of the active site of
sulfatases. In MLD mutations in the
arylsulfatase A (ARSA) gene cause
ARSA deficiency with subsequent accumulation of 3-sulfogalactocerebroside especially in oligodendrocytes. The clinical consequence is
demyelination and a devastating neurological disease.
Enzyme replacement therapy (ERT) with recombinant human
arylsulfatase A (rhARSA), gene therapy, and
stem cell transplantation are suggested as new therapeutic options. The aim of our study was to characterize rhARSA concerning its substrate specificity using analytical isotachophoresis (
ITP). Substrate specificity could be demonstrated by
sulfate splitting from the natural substrates 3-sulfogalactocerebroside and ascorbyl-2-sulfate and the artificial substrate p-nitrocatecholsulfate, whereas galactose-6-sulfate, a substrate of galactose-6‑sulfurylase, was totally resistant. In contrast, leukocyte extracts of healthy donors were able to split
sulfate also from galactose-6-sulfate. The
ITP method allows therefore a rapid and simple differentiation between samples of MLD and MSD patients and healthy donors. Therefore, the isotachophoretic diagnostic assay from leukocyte extracts described here provides a fast and efficient way for the diagnosis of MLD and MSD patients and an elegant system to differentiate between these diseases in one assay.