Glycogen Storage Disease Type I

Glycogen storage disease type I (GSD I) is an inherited disease that results in the liver being unable to properly break down stored glycogen. This impairment disrupts the liver’s ability to break down stored glycogen that is necessary to maintain adequate blood sugar levels. GSD I is divided into two main types, GSD Ia and GSD Ib, which differ in cause, presentation, and treatment. GSD Ia is caused by a deficiency in the enzyme glucose-6-phosphatase, while GSD Ib is caused a deficiency in the enzyme glucose-6-phosphate translocase. Since glycogenolysis is the principal metabolic mechanism by which the liver supplies glucose to the body during periods of fasting, both deficiencies cause severe low blood sugar and, over time, excess glycogen storage in the liver and (in some cases) the kidneys.
GSD I patients typically present with an enlarged liver from non-alcoholic fatty liver disease as the result of this glycogen buildup. Other functions of the liver and kidneys are initially intact in GSD I, but are susceptible to a variety of other problems. Without proper treatment, GSD I gives rise to chronic low blood sugar, which can result in derangements including excessive levels of lactic acid and abnormally high levels of lipids in the bloodstream. Frequent feedings of cornstarch or other carbohydrates are the principal treatment for all forms of GSD I.
GSD Ib also features chronic neutropenia due to a dysfunction in the production of neutrophils in the bone marrow. This immunodeficiency, if untreated, makes GSD Ib patients susceptible to infection. The principal treatment for this feature of GSD Ib is filgrastim; however, patients often still require treatment for frequent infections, and a chronically enlarged spleen is a common side effect. GSD Ib patients often present with inflammatory bowel disease.It is the most common of the glycogen storage diseases. GSD I has an incidence of approximately 1 in 100,000 births in the American population, and approximately 1 in 20,000 births among Ashkenazi Jews. The disease was named after German doctor Edgar von Gierke, who first described it in 1929.