Metachromatic leukodystrophy is a hereditary
neurodegenerative disorder in man associated with deficient
arylsulfatase-A activity (
aryl-sulfate sulfohydrolase, EC 3.1.6.1). The same
enzyme deficiency has been noted in clinically normal individuals, a condition known as
pseudo arylsulfatase-A deficiency. With a nonselective method, somatic cell hybrids were obtained from cultured fibroblasts of these two types of individuals; the hybrids showed no restoration of
arylsulfatase-A activity. Thus,
metachromatic leukodystrophy and
pseudo arylsulfatase-A deficiency are allelic conditions. Although these conditions cannot be distinguished by simple quantitative
arylsulfatase-A activity assays, they can be differentiated with
sucrose density gradient centrifugation, Cellogel electrophoresis, or isoelectric focusing in
polyacrylamide gels. In each case, a small amount of activity with characteristics of
arylsulfatase-A was found only from fibroblasts of
pseudo arylsulfatase-A-deficient individuals and not from those of
metachromatic leukodystrophy patients. This residual
enzyme has the same pH optimum, heat stability, inhibitor sensitivity, and Km as the normal
enzyme but slightly different isoelectric points. In conclusion, although
pseudo arylsulfatase-A deficiency and
metachromatic leukodystrophy have very different clinical outcomes, they are due to mutations of the same structural gene, coding for
arylsulfatase-A. These two conditions can be differentiated now by simple electrophoretic analysis of the residual
arylsulfatase-A activity.