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Multiple transport protein defects in a patient with glycogen storage disease type 1: GSD 1b/1c beta
R A Hawkins1, K R Kamath, H M Scott
1Department of Clinical Biochemistry, Royal Children's Hospital, Parkville, Australia.
Insights
This study reports the first case of a rare double translocase deficiency causing Glycogen Storage Disease type 1 (GSD 1) in a male infant. The condition involves deficiencies in glucose-6-phosphate and pyrophosphate translocases, impacting glucose metabolism.
Area of Science:
- Biochemistry
- Pediatric Endocrinology
- Metabolic Disorders
Background:
- Glycogen Storage Disease (GSD) type 1 is a group of inherited metabolic disorders affecting glucose metabolism.
- GSD type 1 typically results from defects in the glucose-6-phosphatase (G6Pase) enzyme complex.
- Variants of GSD 1 necessitate thorough investigation of the G6Pase complex and its associated transport proteins.
Observation:
- A male infant presented with vomiting, diarrhea, hypoglycemia, and hepatomegaly at 5 months of age.
- Initial investigations suggested GSD, with elevated liver glycogen and normal GSD enzyme activities.
- Further analysis revealed a deficiency in two transport proteins of the G6Pase complex: glucose-6-phosphate translocase and pyrophosphate translocase.
Findings:
- The patient exhibited a rare double translocase deficiency, identified as GSD 1b/1c beta.
- Kinetic analyses confirmed the double translocase deficiency, with no evidence of inhibitors.
- While hypoglycemia is controlled, the patient experiences growth lag and moderate developmental delay.
Implications:
- This case represents the first documented instance of a double translocase deficiency causing GSD type 1.
- Understanding such rare genetic variants is crucial for accurate diagnosis and management of metabolic disorders.
- Further research into the pathophysiology and long-term outcomes of double translocase deficiencies is warranted.
Abstract:
A male child presented at 5 months of age with vomiting, diarrhoea, hypoglycaemia and hepatomegaly. Histology on a frozen liver biopsy suggested glycogen storage disease (GSD), while biochemical analyses confirmed an elevated glycogen content and normal activities of the GSD enzymes 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 the patient produced no glycaemic response. A second biopsy was obtained and appropriately handled for the investigation of variants of the glucose-6-phosphatase enzyme (G6Pase) complex. Results showed that the patient had a deficiency of two transport proteins of the G6Pase complex, namely glucose-6-phosphate translocase and pyrophosphate translocase, i.e. GSD 1b/1c beta. These results were confirmed by additional kinetic analyses which provided confirmation of the double translocase deficiency. 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 markedly lagging and he is moderately developmentally delayed. Neutropenia 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.