Glycogen and polyglucosan storage diseases

Abstract Glycogen is stored in the liver to maintain blood sugar in between meals. Muscles also store glucose, indeed they contain most of the glycogen in the body, to fuel the muscle function but muscles cannot share it with other tissue, because they lack the glucose-6-phosphatase. Absence of glycogen can be tolerated in children and adults as long as hypoglycemia is kept under strict control. Glycogen synthesis requires glycogen synthase and branching enzymes. Absence of glycogen branching enzyme or very active glycogen synthase makes a longer glucose chain that cannot be synthesized or degraded as efficiently causing the accumulation of abnormal glycogen. This condition is named glycogen storage disease type IV, which has different variants according to the remaining enzyme activity. Blocks in glycolysis or factors increasing glycogen synthase activity also cause polyglucosan or normal glycogen accumulation. Although the exact mechanism is not known, unbranched glycogen accumulates in the deficiency of ubiquitin ligases such as Malin, RBCK1, or phosphatase Laforin. Malin or Laforin deficiency causes very severe Lafora disease. Patients show the symptoms of the disease at 15 years of age and they die in a decade because of the severe epilepsy. On the other hand, RBCK1-deficient patients accumulate abnormal glycogen in muscle and heart, causing cardiopathy and myopathy.