Von Gierke (Type I)
Von Gierke disease, also called glycogen storage disease type I (GSD-I), is an autosomal recessive metabolic disorder caused by a deficiency of glucose-6-phosphatase. Glucose-6-phosphatase plays a key role in both glycogenolysis and gluconeogenesis. During periods of fasting, patients with von Gierke disease have an impaired ability to produce free glucose. This leads to severe hypoglycemia and glycogen build-up. The former may lead to seizures, whereas the latter may lead to hepatomegaly. Additionally, the low levels of circulating glucose lead to low levels of insulin and subsequent hypertriglyceridemia. Moreover, the impairment of gluconeogenesis leads to pyruvate build-up, which impairs the conversion of lactate into pyruvate. This manifests clinically as lactic acidosis, an important finding in acute von Gierke disease. Since lactic acid competes with uric acid for transport in the renal tubules, uric acid also builds up in the body. The uric acid may precipitate in the joints, leading to gout / podagra.