MULTIPLE TRANSPORT PROTEIN DEFECTS IN A PATIENT WITH GLYCOGEN-STORAGE-DISEASE TYPE-1 - GSD 1B 1C(BETA)/

A male child presented at 5 months of age with vomiting, diarrhoea, hy poglycaemia and hepatomegaly. Histology on a frozen liver biopsy sugge sted glycogen storage disease (GSD), while biochemical analyses confir med an elevated glycogen content and normal activities of the GSD enzy mes with the proviso that a variant of GSD 1 should be considered. The patient presented at 9 months of age with severe lactic acidosis and hypoglycaemia, A glucagon tolerance test and galactose load test on th e patient produced no glycaemic response. A second biopsy was obtained and appropriately handled for the investigation of variants of the gl ucose-6-phosphatase enzyme (G6Pase) complex. Results showed that the p atient had a deficiency of two transport proteins of the G6Pase comple x, namely glucose-6-phosphate translocase and pyrophosphate translocas e, i.e. GSD 1b/1c(beta). These results were confirmed by additional ki netic analyses which provided confirmation of the double translocase d eficiency. Evidence for inhibitors to these translocases was not found . The patient's treatment has resulted in the hypoglycaemia now being well controlled; however, at 3 years of age, height and weight are mar kedly lagging and he is moderately developmentally delayed. Neutropeni a has not been found and neutrophil function is normal. Double enzyme deficiencies are very rare and possible explanations which might lead to this phenotype are considered. This, to the authors' knowledge, is the first report of a double translocase deficiency causing GSD type 1 .