Glycogen storage disease type 1b: microsomal glucose-6-phosphatase system in two patients with different clinical...

The basic defect in glycogen storage disease (GSD) type 1b was investigated in two patients: one, (Y.S.), a severely affected infant and the other, (Y.M.), an adult with mild clinical symptoms. The enzymatic studies on liver needle biopsy specimens from the two patients indicated that glucose-6-phosphate (G-6-P) phosphohydrolase activity of the "intact microsomes" was partially deficient (20% of that in controls) in Y.M. and undetectable in Y.S. Activities of G-6-P phosphohydrolase in the disrupted microsomes of Y.S. and Y.M. are higher than those in the disrupted microsomes of controls (12.60 mumole/min/g liver in Y.S., 9.18 in Y.M. and 6.26 +/- 1.22, mean +/- S.D. in controls). Our study also shows that PPi phosphohydrolase activities of the "intact microsomes" from both patients (6.07 mumol/min/g liver in Y.S. and 5.36 in Y.M.) were greater than those of the controls (3.23 +/- 0.77 mumole/min/g wet weight liver). These results indicate that the G-6-P translocase was the locus of the defect in both patients with GSD type 1b. Clinical symptoms and enzymatic studies suggest that the clinical severity of this disorder depends on the level of residual activities of G-6-P translocase. Kinetic studies showed an abnormally high Km of the residual G-6-P translocase in Y.M., suggesting a structural gene mutation. The systematic assay method for glucose-6-phosphatase system, which requires only 15 mg of liver tissues, is also described.