Glycogen storage disease type I

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Glycogen storage disease type I (GSD I) or von Gierke’s disease, is the most common of the glycogen storage diseases. This genetic disease results from deficiency of the enzyme glucose-6-phosphatase. This deficiency impairs the ability of the liver to produce free glucose from glycogen and from gluconeogenesis. Since these are the two principal metabolic mechanisms by which the liver supplies glucose to the rest of the body during periods of fasting, it causes severe hypoglycemia. Reduced glycogen breakdown results in increased glycogen storage in liver and kidneys, causing enlargement of both. Both organs function normally in childhood but are susceptible to a variety of problems in the adult years. Other metabolic derangements include lactic acidosis and hyperlipidemia. Frequent or continuous feedings of cornstarch or other carbohydrates are the principal treatment. Other therapeutic measures may be needed for associated problems.

It is named for Edgar von Gierke.[1][2]

Glucose-6-phosphatase is an enzyme located on the inner membrane of the endoplasmic reticulum. The catalytic unit is associated with a calcium binding protein, and three transport proteins (T1, T2, T3) that facilitate movement of glucose-6-phosphate (G6P), glucose, and phosphate (respectively) into and out of the enzyme.

The most common forms of GSD I are designated GSD Ia and GSD Ib, the former accounting for over 80% of diagnosed cases and the latter for less than 20%. A few rarer forms have been described. GSD Ia results from mutations of G6PC, the gene for glucose-6-phosphatase. G6PC is located on chromosome 17q21. GSD Ib results from mutations of the gene for T1, the G6P transporter. The metabolic characteristics of GSD Ia and Ib are quite similar, but Ib incurs a few additional problems (described below).

GSD Ia is inherited as an autosomal recessive disease. Heterozygote carriers (parents) are asymptomatic. As for other autosomal recessive diseases, the recurrence risk for each subsequent child of the same parents is 25%. Prenatal diagnosis has been made by fetal liver biopsy at 18-22 weeks of gestation, but no fetal treatment has been proposed. Prenatal diagnosis is possible with fetal DNA obtained by chorionic villus sampling when a fetus is known to be at risk.

GSD Ia has an incidence in the American population of approximately 1 in 100,000 to 200,000 births. None of the glycogenoses are currently detected by standard or extended newborn screening.

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