Contributor: Gordon K. Klintworth
Glycogenosis type Ia (glycogen storage disease type I, von Gierke disease,  glycogenosis type Ia, glycogen storage disease type Ia, hepatocellular form of glycogen storage disease, hepatorenal form of glycogen storage disease,glucose-6-phosphatase deficiency, hepatorenal glycogenosis)is one of many inherited glycogen storage diseases. It is the original type of glycogenosis type I. It has an autosomal recessive mode of inheritance and is due to mutations in the G6PC gene. The metabolic defect results from a deficiency in glucose-6-phosphatase). Major clinical features of this disorder are massive hepatomegaly, short stature, and enlarged kidneys. It is one of the most severe forms of glycogen storage disease and is accompanied by hypoglycemia, hyperuricemia, hyperlipemia, and hyperlacticacidemia. The hyperuricemia results from both decreased renal tubular secretion of  uric acid, and increased uric acid production by the liver and other tissues. The latter may be a consequence of diminished levels of inorganic phosphate and ATP in the tissues, which secondarily leads to an enhanced breakdown of adenine nucleotides. Hyperuricemia may also be a sequel to increased shunting of  glucose-6-phosphate through the pentose phosphate pathway with an excessive production of ribose-5-phosphate and increased purine synthesis. Ocular abnormalities have been recognized in some patients with glycogenosis type I, but they are mild and not well-documented. Multiple bilateral yellowish paramacular lesions have been identified in some cases, but without an impairment of vision. A faint brown cloudy infiltration invading the cornea from the periphery has also been reported in one case. Since its initial description four variants of glycogenosis type I have been recognized. The original disorder is now known as glycogenosis type Ia. The other types are glycogenosis type Ib, glycogenosis type Ic, and glycogenosis type Id. Glycogenesis type Ib, glycogenesis type Ic and glycogenesis type Id result from  mutations in a different gene to glycogenosis type Ia, namely the G6PT1 gene and this causes a defect in the glucose-6-phosphate transporter.