Prenatal diagnosis of glycogen storage disease type 1a by direct mutation detection

Current laboratory diagnosis for glycogen storage disease type la (GSD la) is established by functional enzyme assay to demonstrate the deficiency of glucose-6-phosphate phosphatase (G6Pase). This procedure requires liver biopsy and is impractical for routine prenatal diagnosis owing to the high morbidity of fetal liver biopsy. The accuracy of test results is dependent on the stability of the enzyme during specimen collection, shipment, and storage. Recently the gene for G6Pase has been cloned and the prevalent mutations in different ethnic groups have been identified. We have developed an allele-specific oligonucleotide (ASO) method to detect mutations in a large number of GSD1a patients. In this paper we report the prenatal detection of mutations in the G6Pase gene using this simple, dependable, rapid, and non-invasive procedure. The turnaround time of this test can be as short as 48 h. A fetus was found to be a carrier using the ASO method and this was confirmed after birth. To our knowledge, this is the first GSD la prenatal case diagnosed by a DNA molecular method.