Prenatal Mucopolysaccharidosis II (Hunter): A Pathogenetic Study

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Abstract
Summary: A prenatal diagnosis of Mucopolysaccharidosis II (M. Hunter) was made early in a pregnancy at risk in a family with one affected child. An affected fetus was diagnosed on the basis of an abnormal incorporation and degradation of 35SO4 in 35SO4-labeled muco-polysaccharides in cultured amniotic cells. Dermatan sulfate and heparin sulfate concentrations in the supernatant of the amniotic fluid were high. In the aborted fetus, the diagnosis could be confirmed by 36S04 incorporation studies in the cultured fibroblasts and in cultured brain cells as well as by the deficiency of the specific enzyme activity (iduronide sulfate sulfatase) in the organs of the fetus. j3-Galactosidase was in the low normal range in liver and spleen but significantly reduced in brain. Under electron microscopy, the mesenchymal cells of liver and spleen showed lysosomal storage of material, presumably mucopolysaccharides, in excess of normal. In the neurons of the spinal ganglia and spinal cord, "Zebra bodies" in statu nascendi were observed. Speculation: Primary and secondary effects of the deficiency in iduronide sulfate sulfatase in the severe form of mucopolysaccharidosis I1 can be demonstrated in the affected fetus as early as the 22nd wk of gestation. In the fetal brain, an inhibition of 8-galactosidase by the accumulating mucopolysaccharides leads to a secondary accumulation of gangliosides in ultrastructurally visible lysosomal "Zebra bodies."