INHERITED DISORDERS OF CARBOHYDRATE-METABOLISM IN CHILDREN STUDIED BY C-13-LABELED PRECURSORS, NMR AND GC-MS

Glucose carbon recycling, glucose production and glucose turnover in glycogen storage disease type I and type II patients and control subjects were determined by a novel approach - mass isotopomer analysis of plasma13C glucose. Changes in the isotopomer distribution of plasma13C glucose were found only in glycogen storage disease type III patients and control subjects. Glucose carbon recyling parameters were also derived from13C NMR spectra of plasma glucose C-1 splitting pattern. Our results eliminate a mechanism for glucose production in glycogen storage disease type I children involving gluconeogenesis. However, glucose release by amylo-1,6-glucosidase activity is in agreement with our results. A quantitative determination of the metabolic pathways of fructose conversion to glucose in normal children, and in children with disorders of fructose metabolism was derived from13C NMR measurement of plasma13C glucose isotopomer populations following [U-13C]fructose administration. A direct pathway from fructose, bypassing fructose-1-phosphate aldolase, to fructose-1,6-diphosphate in controls and hereditary fructose intolerant children (47% and 27%, respectively) was identified. In children with fructose-1,6-diphosphatase deficiency, only the gluconeogenic substrates were13C labelled but no synthesis of glucose from [U-13C]fructose occurred. The significantly lower (by 68%) conversion of fructose to glucose in hereditary fructose intolerance, as compared to control subjects, and non-conversion in fructose-1,6-diphosphatase deficient subjects after [U-13C]fructose (∼ 20 mg/kg) administration can serve as the basis of a safe diagnostic test for patients suspected of inborn errors of fructose metabolism and other defects involving gluconeogenesis. © 1990 SSIEM and Kluwer Academic Publishers.