GLUCOSE-6-PHOSPHATASE DEFICIENCY GLYCOGEN STORAGE DISEASE

Abstract

Three siblings with glycogen storage disease have been studied. These children demonstrated the classic physical findings of von Gierke's disease. Liver enzyme assays on one sibling revealed very low glucose 6-phosphatase activity. Hepatic phosphoglucomutase, phosphorylase, glucose 6-phosphate dehydrogenase, and fructose 1,6-diphosphatase activities were within normal limits. Erythrocyte glucose 6-phosphate dehydrogenase activity was also normal. Incubation of liver slices with glucose 1-C14 and glucose 6-C14 revealed an initial rate of C14O2 production at which CO2 from C-1 was three times that from C-6. This is strong evidence for the active operation of the phosphogluconate oxidation pathway in this patient, and taken with the normal assay value of hepatic glucose-6-phosphate dehydrogenase, constitutes a negation of the concept of a dual enzyme defect recently proposed for von Gierke's disease. Striking elevations of free fatty acids in serum, triglycerides, phospholipids, cholesterol, and blood ketones were noted. Potential mechanisms for these elevations have been discussed. Marked hyperuricemia was a persistent finding and was associated with a somewhat low renal clearance of urate in the one patient studied. All three had striking elevations of lactic acid in blood, which is known to interfere with renal urate excretion. Thus renal factors may have contributed to the hyperuricemia, previously considered solely a consequence of enhanced nucleoprotein catabolism secondary to persistent hypoglycemia. Long-term intramuscular administration of glucagon did not produce significant clinical or laboratory improvement in the one patient in whom it was employed.