A girl presented with an important growth retardation, hepatomegaly, fasting hypoglycemia, lactic acidosis, increased serum cholesterol, triglycerides and uric acid, and increased liver glycogen (7.5%). There was no rise in blood glucose after IV galactose or fructose, but glucagon gave a delayed response. Type Ib glycogen storage disease was suggested by the low normal activity of glucose-6-phosphatase (G-6-Pase) which reached 1.8 units/g (normal, 2 to 10 units/g) and the normal activity of other glycogenolytic enzymes, measured in homogenates prepared in H2O (mean +/- S.E. in control subjects: 59% +/- 7; in type Ia GSD: 92% +/- 3). The activity of G-6-Pase measured as described above increased to 3.8 units/g of liver 1 year after PCS and 7.85 units/g of liver after 3 years. At that time, a simultaneous assay of the enzyme in a fresh, previously not frozen liver biopsy, homogenized in 0.25 M sucrose, revealed only about 29% of the activity of the same sample prepared in H2O (mean +/- S.E. in three controls: 95.8% +/- 8.9.

Clinical and biochemical findings before and after portacaval shunt (PCS) in type Ib glycogen disease (GSD). An 11-year-old girl with statural age of 5 yrs. and hepatomegaly (15cm) had fasting hypoglycaemia, acidosis, increased serum cholesterol, triglycerides and uric acid, and increased liver glycogen (7.5%). There was no rise in blood glucose after i.v.galactose or fructose but glucagon gave a delayed response. Type Ib GSD was suggested by the normal activity of glucose-6-phosphatase (G-6-Pase) and of other glycogenolytic enzymes in frozen liver. After PCS, at 12 6/12 yrs., height increased by 29cm in 3 yrs. Serum cholesterol decreased from 620 to 230mg/dl and triglycerides from 2400 to 200mg/dl. At oral GTT peak values for glucose (mg/dl) and insulin (U/1) were respectively 210 and 50 before, 290 and 90 after PCS. Higher than normal utilisation of (2-3H,U-14C)-glucose was shown by a 3H/14C ratio of 24% after 60 min.(mean ± S.E.M.: 59% ± 7 in normals and 92% ± 3 in type Ia GSD) and can be explained by peripheral hyperinsulinism. Assay of G-6-Pase in a fresh liver homogenate prepared in 0.25 M-sucrose revealed only 29% (96% ± 11 in 3 controls) of the enzyme activity as compared with an homogenate in H2O. The latter finding may be in favour of the hypothesis of Narisawa et al. (Biochem. Biophys. Res.Comm. 83: 1360, 1978) postulating a defect of the microsomal G-6-transport system in type Ib GSD, but is difficult to reconcile with the isotopic data.