Rapid prenatal diagnosis of glycogen-storage disease type II by electron microscopy of uncultured amniotic-fluid cells.

Glycogen-storage disease Type IIa is a fatal, genetically determined disease of infancy or early childhood that is characterized by deficient activity of acid alpha-glucosidase and by the presence of intracellular vacuoles full of glycogen, which are found in most tissues, including skin and liver. On electron microscopy these specific vacuoles are tightly packed accumulations of glycogen particles surrounded by a single membrane. We did electron-microscopical examinations on uncultured amniotic-fluid cells from 26 women whose fetuses were at risk for glycogen-storage disease Type IIa and from 8 normal control pregnant women. We found specific vacuoles in cells from 6 of the 26 high-risk patients. At delivery, glycogen-storage disease Type IIa was present in the infants of these 6 women and absent in those of the other 20 according to results of clinical, biochemical, and electron-microscopical studies of gestational products. After amniocentesis at 15 to 18 weeks of gestation, the prenatal diagnosis made by electron microscopy of uncultured amniotic-fluid cells was available in three to six days, whereas it took from three to six weeks to make the diagnosis by enzymatic analysis of the cultured amniotic-fluid cells. We conclude that the electron-microscopical prenatal diagnosis of glycogen-storage disease Type IIa is rapid, safe, and reliable. It should facilitate earlier diagnosis and thereby help to preserve parental options.