General description

Glycogen storage disease type I (GSD I), also known as von Gierke disease, is a rare inherited metabolic disorder characterized by the accumulation of glycogen and fat in various organs, primarily the liver and kidneys. GSD I is an autosomal recessive disorder caused by deficiencies in specific enzymes involved in the glycogen metabolism pathway. It comprises two major subtypes: GSD Ia and GSD Ib. GSD Ia results from a deficiency of the glucose-6-phosphatase (G6Pase) enzyme, which normally cleaves glycogen to glucose. This enzyme plays a crucial role in the final step of both gluconeogenesis and glycogenolysis, converting glucose-6-phosphate to glucose. GSD Ib, on the other hand, is characterized by normal G6Pase activity but deficiency in the glucose-6-phosphate translocase (G6PT), which transports glucose-6-phosphate from the cytoplasm into the endoplasmic reticulum for hydrolysis.

The clinical presentation of GSD I typically begins in infancy when feeding intervals extend to 3-4 hours, with manifestations varying in age of onset, progression rate, and severity. The cardinal features include hypoglycemia, lactic acidosis, hyperlipidemia, hyperuricemia, hepatomegaly, and growth retardation. Severely affected infants may present in the neonatal period with profound hypoglycemia, while more commonly, infants present at 3-4 months of age with hepatomegaly and severe hypoglycemia, with or without seizures.

Long-term complications of untreated or inadequately managed GSD I include hepatic adenomas with malignant potential, renal disease (including proximal and distal renal tubular acidosis, nephrocalcinosis, and kidney failure), gout, systemic and pulmonary hypertension, osteoporosis, delayed puberty, pancreatitis, and polycystic ovaries. Platelet dysfunction and abnormal von Willebrand factor may lead to bleeding tendencies, including frequent epistaxis and menorrhagia in females. Prolonged hypoglycemic episodes can result in seizures and cognitive impairment.