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ABSTRACT

  • Glycogen storage diseases are inherited disorders that affect glycogen metabolism. Virtually all proteins involved in the synthesis or degradation of glycogen and its regulation have been discovered to cause some type of glycogen storage disease. The glycogen found in these disorders is abnormal in quantity, quality, or both. The different forms of glycogen storage disease have been categorized by number in accordance with the chronological order in which these enzymatic defects were identified. Liver and muscle have abundant quantities of glycogen and are the most commonly and seriously affected tissues. Because carbohydrate metabolism in the liver is responsible for plasma glucose homeostasis, glycogen storage diseases that mainly affect the liver usually have hepatomegaly and hypoglycemia as the presenting features. In contrast, the role of glycogen in muscle is to provide substrates for the generation of ATP for muscle contraction. The predominant clinical features of glycogen storage diseases that mainly affect the muscle are muscle cramps, exercise intolerance, susceptibility to fatigue, and progressive weakness.

  • Type Ia glycogen storage disease, or von Gierke Disease (MIM 232200), is caused by a deficiency of glucose 6-phosphatase activity in the liver, kidney, and intestinal mucosa, with excessive accumulation of glycogen in these organs. The stored materials in the liver include both glycogen and fat. The clinical manifestations are growth retardation, hepatomegaly, hypoglycemia, lactic acidemia, hyperuricemia, and hyperlipidemia. A variant caused by a defect in the transport of glucose 6-phosphate (type Ib) (MIM 232200) has the additional findings of neutropenia and impaired neutrophil function, resulting in recurrent bacterial infections and oral and intestinal mucosa ulceration. Both type Ia and Ib genes have been cloned and mutations responsible for the diseases identified. In the past, many patients with type I glycogen storage disease died, and the prognosis was guarded in those who survived. Long-term complications include gout, hepatic adenomas, osteoporosis, renal disease, and short stature. Major progress has been made in managing this disorder. The current treatment of type I glycogen storage disease is nocturnal nasogastric infusion of glucose or orally administered uncooked cornstarch. Both methods are effectively improving growth, reducing hepatomegaly and sustaining the commonly measured metabolic indexes of adequate therapy in patients with type I glycogen storage disease. Early diagnosis and early initiation of an effective treatment have improved the outcome of the disease, but it is not known if all long-term complications can be avoided by good metabolic control. Some early treated patients who are now adults still develop hepatic adenomas and proteinuria.

  • Type II glycogen storage disease, also known as Pompe Disease (MIM 232300), is caused by a deficiency of lysosomal acid α-glucosidase and is the prototype of an inborn lysosomal storage disease. This disease is described in Chap. 171.

  • Type III glycogen storage disease (MIM 232400) is caused by a deficiency of glycogen debranching enzyme activity. A deficiency of debranching enzyme impairs the release of glucose from glycogen but does not affect glucose released from gluconeogenesis. The glycogen accumulated has a structure that ...

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