PRENATAL-DIAGNOSIS OF GLYCOGEN-STORAGE-DISEASE TYPE IA BY RESTRICTIONENZYME DIGESTION

Glycogen storage disease type Ia (GSD Ia) is an autosomal recessive co ndition, caused by a deficiency of hepatic glucose-6-phosphatase (G6Pa se) activity. In a consanguineous family originating from northern Afr ica whose first daughter was affected with GSD Ia, we were able to ide ntify the disease-causing mutation, a cytosine to thymine substitution at nucleotide 326 in exon 2 of the G6Pase gene (R83C). This mutation causes the disappearance of an HgaI site, and is thus easily detectabl e by restriction enzyme digestion. Both parents were heterozygous for this mutation. During the third pregnancy, fetal genomic DNA was extra cted from a chorionic villus biopsy sampled at the 24th week of gestat ion. Exons 2 of the G6Pase gene were amplified by the polymerase chain reaction followed by HgaI digestion. Fetal DNA analysis indicated tl- lat the fetus had received both normal C6Pase alleles. This result was confirmed after birth. DNA analysis is the only reliable method for p renatal diagnosis of GSD Ia. (C) 1998 John Wiley & Sons, Ltd.