Prenatal diagnosis of metachromatic leukodystrophy by electrophoretic and immunologic techniques

Electrophoretic examination of extracts of cultured amniotic fluid cells from a pregnancy at risk for metachromatic leukodystrophy (MLD) showed absence of arylsulfatase A (AS-A) activity. Immunodiffusion with anti-human AS-A immune serum failed to show enzymatically active arcs of immune precipitate. Electrophoretic studies and quantitative assay of extracts of organs from the aborted fetus confirmed the diagnosis of MLD. Electrophoresis of amniotic fluid from this and one additional fetus with MLD showed an arylsulfatase pattern qualitatively and quantitatively indistinguishable from normal. In both normal and MLD fluids, the AS-A band was replaced by a band with lower anodal mobility. Only the anodal band of normal amniotic fluid, however, reacted with the anti-AS-A immune serum in immunoelectrophoresis. Assay of amniotic fluic with p-nitrocatechol sulfate (PNCS) as a substrate showed marked deficiency of "AS-A" activity in the fluids from the two MLD pregnancies. An optimal procedure for prenatal detection of MLD should include electrophoresis of extracts of cultured amniotic fluid cells with visual demonstration of absence of AS-A activity. Immunologic techniques applied to cell-free amniotic fluid may be of help in the rapid identification of the fetal genotypes.