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.
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
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