Prenatal diagnosis and carrier detection for glycogen storage disease type III using polymorphic DNA markers

Deficiency of glycogen debranching enzyme gene (AGL) causes glycogen storage disease type III (GSD-III), an autosomal recessive disease. Prenatal diagnosis and carrier detection using enzymatic methods are technically difficult and have limited ability to distinguish a carrier from an affected patient. Mutations in the AGL gene can be used for these purposes. However, the mutations identified thus far account for less than half of the total mutant alleles, and no common mutations have been detected except in North African Jews and in a rare subtype of the disease (GSD-IIIb). Our recent identification of three highly informative DNA polymorphic markers in the AGL gene allowed us to perform prenatal diagnosis and carrier detection in two GSD-III families with unknown mutations, using the polymerase chain reaction (PCR) and restriction analysis. In one family, a fetus was diagnosed to be a GSD-III carrier and his carrier status was confirmed postnatally. A newborn in the second family was postnatally diagnosed with the disease.