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Prenatal mucopolysaccharidosis II (Hunter): a pathogenetic study
Abstract:
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 mucopolysaccharides 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 35SO4 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. beta-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.
Insights
Prenatal diagnosis of Mucopolysaccharidosis II (M. Hunter syndrome) was achieved using amniotic cell analysis. This rare genetic disorder involves abnormal mucopolysaccharide metabolism, confirmed by enzyme deficiency in the fetus.
Area of Science:
- Medical Genetics
- Biochemistry
- Developmental Biology
Background:
- Mucopolysaccharidosis II (M. Hunter syndrome) is a rare X-linked genetic disorder.
- It results from deficient iduronate-2-sulfatase activity, leading to mucopolysaccharide accumulation.
- Early diagnosis is crucial for potential management and family planning.
Purpose of the Study:
- To describe the successful prenatal diagnosis of Mucopolysaccharidosis II.
- To detail the diagnostic methods employed in a high-risk pregnancy.
- To characterize the biochemical and cellular findings in an affected fetus.
Main Methods:
- Prenatal diagnosis via cultured amniotic cells analyzing 35SO4 incorporation and degradation.
- Measurement of dermatan sulfate and heparin sulfate in amniotic fluid.
- Enzyme activity assays (iduronate-2-sulfatase, beta-galactosidase) in fetal tissues.
- Electron microscopy of fetal cells (fibroblasts, brain cells, spinal ganglia).
Main Results:
- Abnormal 35SO4 metabolism confirmed Mucopolysaccharidosis II in cultured amniotic cells.
- Elevated dermatan sulfate and heparin sulfate levels were detected in amniotic fluid.
- Deficiency of iduronate-2-sulfatase activity was found in fetal organs.
- Electron microscopy revealed lysosomal storage and nascent 'Zebra bodies' in fetal neurons.
Conclusions:
- Prenatal diagnosis of Mucopolysaccharidosis II is feasible using biochemical and cellular analyses.
- Fetal tissue examination confirmed the diagnosis and provided insights into cellular pathology.
- This case highlights the importance of early detection in families with a history of M. Hunter syndrome.