Monday, November 19, 2012

GLYCOGEN STORAGE DISEASE


Glycogen storage diseases are the result of deficiency of enzymes that cause the alteration of glycogen metabolism. The liver forms (type I, III, IV and VI) are marked by hepatomegaly due to increased liver glycogen and hypoglycemia caused by inability to convert glycogen to glucose. The muscle forms (type II, IIIA, V and VII) have mild symptoms appearing during sternous exercise owing to inability to provide energy for muscle contraction.



Type 0 (Glycogen synthase deficiency)

There is hypoglycemia; hyperketonemia and early death.

Type I (Glucose-6-phosphatase deficiency)-Von Gierke’s disease

This is the most common autosomal recessive disease. This disease is characterized by severe hypoglycemia that coincides with metabolic acidosis, ketonemia and elevated lactate (due to excess glycolysis) and alanine. Hypoglycemia occurs because glycogen cannot be converted back to glucose. A glycogen build up is found in liver causing hepatomegaly. The patients have severe hypoglycemia, hyperlipidemia (increased lipolysis caused by decreased glucose), uricemia (caused by competitive inhibition by lactate of renal tubular urate secretion and increased uric acid production) and growth retardation. Glucagon and epinephrine cannot produce hyperglycemia but result in increased lactate concentration and lipolysis. A variant of the disease type IB has been identified as a defect in endoplasmic reticulum glucose-6-phosphatase transport system. Other forms include a defect in microsomal phosphate or pyrophosphate transport (type IC) and defect in microsomal glucose transport (type ID).

Type II (Lysosomal α1->4 and α1->6 Glucosidase deficiency)- Pompes disease

It affects predominantly the heart and skeletal muscle, producing muscle weakness and cardiomegaly. Liver function is normal and patients do not have hypoglycemia. Two forms identified; (1) infantile (pompes disease) that develop in first few months of life with weakness and respiratory difficulties and (2) juvenile that is present in second or third decade of life with difficulty in walking.

Type III (Amylo-1,6-Glucosidase deficiency)-Forbe’s or Cori’s disease

Deficiency of glycogen debranching enzyme results in storage of an abnormal form of glycogen (limit dextrinosis). Both liver and muscle are affected (type IIIA), producing hepatomegaly and muscle weakness. About 15% have only liver involvement (Type IIIB). Differentiation from type I is by hyperglycemic response to galactose, low concentration of urate and lactate in blood, and elevated serum transaminases and creatinine kinase activities.

Type IV (Branching Enzyme deficiency)-Andersons disease of Amylopectinosis

It is extremely rare disorder manifested by production of an abnormal form of unbranched glycogen in all tissue. Patients exhibit hepatospleenomegaly with ascites and liver failure. There is death from heart or liver failure before 5 years of age.

Type V (Muscle Phosphorylase deficiency)-McArdle’s disease

It is also called McArdle’s disease usually present in second or third decade with muscle cramps after exercise. Increased plasma creatine kinase activity at rest, failure of ischemic exercise to increase serum lactate concentrations while producing an exaggerated increase in ammonia, moglobinuria and diminished activity of muscle phosphorylase establish the diagnosis.

Type VI (Liver phosphorylase deficiency)- Hers’ disease

It manifest as hepatomegaly caused by increased deposits of normal glycogen in liver or in red or white blood cells.

Type VII (Muscle and erythrocyte phosphofructokinase deficiency)-Taruis’ disease

Patients have abnormal glycogen in muscle. Exercise intolerance, unresponsiveness to glucose administration, and hemolysis (caused by decreased glycolysis in RBC) are noted clinically, producing hyperbilirubinemia, pigmenturia and reticulocytosis.

Type VIII (Liver phosphorylase kinase deficiency)
Type IX (Liver and muscle phosphorylase kinase deficiency)
Type X (cAMP dependent protein kinase A deficiency)

There is hepatomegaly and glycogen accumulation in liver