📖 Biochemistry

A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by enzyme deficiencies affecting either glycogen synthesis, glycogen breakdown or glycolysis (glucose breakdown), typically in muscles and/or liver cells. GSD has two classes of cause: genetic and acquired.

Mnemonic:VP CAM HT.– Very Poor Carbohydrate Affects Muscle and Hepatic Target.

1. Type I – Von Gierke’s disease
2. Type II – Pompe’s disease
3. Type III – Cori’s disease
4. Type IV – Anderson’s disease
5. Type V – McArdle’s disease
6. Type VI – Her’s disease
7. Type VII – Tauri’s disease

Type 0 (Glycogen synthase deficiency)

There is hypoglycemia; hyperketonemia and early death.

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

- most common autosomal recessive disease.
- characterized by severe hypoglycemia that coincides with metabolic acidosis,
- ketonemia and elevated lactate (due to excess glycolysis) and alanine

 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

- 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

- Increased plasma creatine kinase activity at rest,
- failure of ischemic exercise to increase serum lactate concentrations while producing an exaggerated increase in ammonia,

- myoglobinuria 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

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