PRENATAL-DIAGNOSIS OF THE CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME TYPE 1A (CDG1A) BY A COMBINATION OF ENZYMOLOGY AND GENETIC-LINKAGE ANALYSIS AFTER AMNIOCENTESIS OR CHORIONIC VILLUS SAMPLING

Two pregnancies at risk for the carbohydrate-deficient glycoprotein sy ndrome Type 1A (CDG1A: phosphomannomutase deficient) were monitored by enzyme and genetic linkage analyses. The index case in both families had a proven deficiency of phosphomannomutase (PMM). An unaffected fet us was predicted in family 1 following amniocentesis. Normal PMM activ ity was found in cultured amniotic fluid cells and there was no elevat ion of lysosomal enzymes in the amniotic fluid. Genetic linkage analys is using microsatellite markers closely linked to the CDG1A gene confi rmed this prediction. A healthy child was born. In the second family d irect assay of chorionic villi showed a profound deficiency of PMM and genetic linkage analysis showed the fetus to have the same haplotype as the proband. The pregnancy was terminated and a deficiency of PMM w as confirmed in cultured fibroblasts from the fetus. Reliable prenatal diagnosis of CDG Type 1A (PMM-deficient) can be achieved by a combina tion of biochemical and molecular genetic tests. (C) 1998 John Wiley & Sons, Ltd.