For example, glucose-6-phosphatase (G6Pase) deficiency in GSD type Ia (GSD Ia) affects primarily the liver and kidney, while acid α-glucosidase (GAA) deficiency in GSD II causes primarily muscle disease.
Although liver biopsy revealed moderate fibrosis with a suggested diagnosis of glycogen storage disease (GSD), no mutations were identified either by single gene approach for GSD (G6PC and GAA) or by next generation sequencing panels for GSD (including 21 genes).
Glycogen storage diseases (GSDs) are characterized by abnormal inherited glycogen metabolism in the liver, muscle, and brain and divided into types 0 to X. GSD type I, glucose 6-phosphatase system, has types Ia, Ib, Ic, and Id, glucose 6-phosphatase, glucose 6-phosphate translocase, pyrophosphate translocase, and glucose translocase deficiencies, respectively.
Demonstration by molecular biology techniques of a mutation in both alleles of the G6Pase gene establishes the diagnosis of GSD Type Ia, obviating the need for a liver biopsy.
Polymerase chain reaction (PCR) and nucleotide sequence analysis were used to identify the location and nature of mutations at the G6Pase locus in two siblings affected with type 1a GSD.
DNA analysis indicated that the fetus was a heterozygous carrier of type Ia GSD with a mutant G6Pase allele at exon 2 and a normal G6Pase allele at exon 5.
Our results show that the G6Pase gene of GSD type 1b and 1c patients is normal, consistent with the translocase-catalytic unit model of G6Pase catalysis.
Sixteen mutations were uncovered that were shown by expression to abolish or greatly reduce G6Pase activity and that therefore are responsible for the GSD type 1a disorder.
The understanding of type 1 glycogen storage diseases (GSDs) has been greatly hindered by a lack of knowledge of the molecular basis of glucose-6-phosphatase (Glc-6-P'ase).
The characterization of the murine glucose-6-phosphatase gene opens the way for studying the molecular basis of GSD type 1a in humans and its etiology in an animal model.
Patients with glycogen storage disease (GSD) type 1b have shown normal activity of glucose-6-phosphatase (EC 3.1.3.9) as assayed in frozen liver, though their clinical and biochemical findings were similar to those of patients with GSD 1a (McKusick 23220) (Senior and Loridan, 1968).