Glycogen Storage Disease

Key Features

• Glycogen is a highly branched polymer of glucose that is stored in liver and muscle

• Different enzyme defects affect its biosynthesis and degradation

• Types 0, I, III, VI, and IX manifest with hypoglycemia in infants

• Types II, V, and VII manifest with rhabdomyolysis or muscle weakness

• Types IV and IX manifest with hepatic cirrhosis

Clinical Findings

• Hepatic forms of the glycogenoses cause

  • Growth failure

  • Hepatomegaly

  • Severe fasting hypoglycemia

• Glycogen synthase deficiency (GSD; glycogen storage disease type 0)

  • Causes hypoglycemia, usually after about 12 hours of fasting

  • Can cause mild postprandial hyperglycemia and hyperlactatemia

• Glycogenosis type IV, brancher enzyme deficiency, usually presents with progressive liver cirrhosis, as do some rare forms of phosphorylase kinase deficiency

• The gluconeogenesis disorder fructose-1,6-bisphosphatase deficiency presents with major lactic acidosis and delayed hypoglycemia on fasting

• Skeletal myopathy with weakness or rhabdomyolysis may be seen in

  • Muscle phosphorylase deficiency (type V)

  • Phosphofructokinase deficiency (type VII)

  • Acid maltase deficiency (type II; Pompe disease)

• Infantile form of Pompe disease also has hypertrophic cardiomyopathy and macroglossia

Diagnosis

• Initial tests include glucose, lactate, triglycerides, cholesterol, uric acid, transaminases, and creatine kinase

• Functional testing includes responsiveness of blood glucose and lactate to fasting

• An ischemic or nonischemic exercise test is helpful for myopathic forms

• Most glycogenoses can be diagnosed by molecular analysis

• Other diagnostic studies include enzyme assays of leukocytes, fibroblasts, liver, or muscle

• Disorders diagnosable from analysis of red blood cells include deficiency phosphorylase kinase (type IX) in half the cases

• Pompe disease can usually be diagnosed by assaying acid maltase in a blood spot with confirmation in fibroblasts

Treatment

• Treatment is designed to prevent hypoglycemia and avoid secondary metabolite accumulations such as elevated lactate in glycogenosis type I

• In GSD1, the special diet must be strictly monitored with restriction of free sugars and measured amounts of uncooked cornstarch, which slowly releases glucose in the intestinal lumen

• Immunomodulation is used for patients whose treatment response declines due to antibodies to the recombinant enzyme