Consisting of at least eight distinct errors of metabolism — all inherited — glycogen storage disease alters the synthesis or degradation of glycogen, the form in which glucose is stored in the body. Normally, muscle and liver cells store glycogen. Muscle glycogen is used in muscle contraction; liver glycogen can be converted into free glucose, which can then diffuse out of the liver cells to increase blood glucose levels. Glycogen storage disease manifests as a dysfunction of the liver, heart, or musculoskeletal system. Symptoms vary from mild and easily controlled hypoglycemia to severe organ involvement that may lead to cardiac and respiratory failure.
Primary clinical features of liver glycogen storage disease (types I, III, IV, VI, and VIII) are hepatomegaly and rapid onset of hypoglycemia and acidosis when food is withheld. Symptoms of muscle glycogen storage disease (types II, V, and VII) include poor muscle tone; type II may result in death from heart failure. In addition, type I may produce the following symptoms: ❑ infants — acidosis, hyperlipidemia, GI bleeding, coma ❑ children — low resistance to infection and, without proper treatment, short stature ❑ adolescents — gouty arthritis and nephropathy; chronic tophaceous gout; bleeding (especially epistaxis); small superficial vessels visible in skin because of impaired platelet function; and fat deposits in cheeks, buttocks, and subcutaneous tissues. Other symptoms include poor muscle tone; enlarged kidneys; xanthomas over extensor surfaces of the arms and legs; steatorrhea; multiple, bilateral, yellow lesions in fundi; and osteoporosis, probably secondary to a negative calcium balance. Proper treatment of glycogen storage disease should prevent all these effects.
Almost all glycogen storage disease (types I through V and type VII) is transmitted as autosomal recessive traits. (See Types of glycogen storage disease.) The mode of transmission of type VI is unknown; type VIII may be an X-linked trait. The most common type of glycogen storage disease is type I, glucose-6-phosphatase deficiency, or von Gierke’s disease, which results from a deficiency of the liver enzyme glucose-6-phosphatase. It occurs in about 1 in 200,000 births, but the incidence may be higher in some populations. This enzyme converts glucose-6-phosphate into free glucose and is necessary for the release of stored glycogen and glucose into the bloodstream to relieve hypoglycemia. Infants may die of acidosis before age 2; if they survive past this age, with proper treatment, they may grow normally and live to adulthood with only minimal hepatomegaly. Brief periods of fasting may produce irritability due to hypoglycemia and acidosis. Perspiration is excessive, and older children show heat intolerance. Easy bruising may be common. In older, untreated children, growth may be slow and sexual development may be incomplete. Hepatic adenomas are commonly seen by adolescence and may be premalignant lesions. Nonsense, deletion, missense, and splice-junction mutations have been found in the gene that encodes the muscular isoform of phosphorylase. The gene is mapped to 11q13 and contains 20 exons. Although mutational heterogeneity exists, the molecular defect results in the near-complete absence of the protein in skeletal muscle in most individuals.
Diagnosis depends on findings from patient history and physical examination, creatine kinase testing, muscle biopsy, electromyelography, and ischemic forearm testing. Biochemical assay for enzyme activity is the method of definitive diagnosis.
For type I, the aims of treatment are to maintain glucose homeostasis and prevent secondary consequences of hypoglycemia through frequent feedings and a constant nocturnal nasogastric (NG) drip with an enteral nutrition formula or dextrose. Uncooked cornstarch is given and acts as a slow-release form of glucose. Treatment includes a low-fat diet with normal amounts of protein and calories; carbohydrates should contain glucose or glucose polymers only. Therapy for type III includes frequent feedings and a high-protein diet. Type IV requires a high-protein, high-calorie diet; bed rest; diuretics; sodium restriction; and paracentesis, if necessary, to relieve ascites. Types V and VII require no treatment except avoidance of strenuous exercise. No treatment is necessary for types VI and VIII, and no effective treatment exists for type II.