Glycogen storage disease due to glucose-6-phosphatase deficiency

Glycogen storage disease due to glucose-6-phosphatase deficiency, also known as Glycogen Storage Disease type I (GSD I) or von Gierke disease, is a rare inherited metabolic disorder caused by deficiency of the glucose-6-phosphatase enzyme system. This enzyme is essential for the final step of gluconeogenesis and glycogenolysis, which releases free glucose from the liver into the bloodstream. When this enzyme is deficient, glycogen and fat accumulate abnormally in the liver, kidneys, and intestinal mucosa. There are two main subtypes: GSD Ia (caused by mutations in the G6PC gene encoding glucose-6-phosphatase catalytic subunit) and GSD Ib (caused by mutations in the SLC37A4 gene encoding the glucose-6-phosphate translocase). The disease primarily affects the liver and kidneys but has multisystemic consequences. Key clinical features include severe fasting hypoglycemia, hepatomegaly (enlarged liver), growth retardation, lactic acidosis, hyperuricemia, hyperlipidemia, and a characteristic rounded "doll-like" facial appearance. Patients with GSD Ib additionally suffer from neutropenia and recurrent bacterial infections, as well as inflammatory bowel disease-like symptoms. Hypoglycemia can occur within hours of fasting and may lead to seizures if untreated. Long-term complications include hepatic adenomas (with potential for malignant transformation), renal disease including focal segmental glomerulosclerosis, osteoporosis, and pulmonary hypertension. Treatment is primarily dietary, centered on maintaining blood glucose levels through frequent meals, continuous nocturnal gastric drip feeding in infants, and uncooked cornstarch supplementation in older children and adults to provide a slow-release source of glucose. Dietary management also involves restricting fructose, galactose, and sucrose intake. For GSD Ib, granulocyte colony-stimulating factor (G-CSF) is used to manage neutropenia, and empagliflozin has shown promise in treating neutropenia and inflammatory bowel symptoms. Liver transplantation may be considered in severe cases with poor metabolic control or hepatocellular carcinoma. With proper dietary management, patients can achieve improved growth and quality of life, though lifelong monitoring for complications is essential.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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