6. Abnormal intracellular glycogen accumulations. Glycogenoses.

Abnormal intracellular glycogen accumulations. Glycogenoses

One of the common forms of reversible cellular injury is the abnormal accumulation of substances in cells, common intracellular accumulations can be:

• Glycogen
• Proteins
• And Pigments (both exogenous and endogenous)

Excessive intracellular deposits of glycogen are associated with metabolism abnormalities of glucose or glycogen. Such glucose or glycogen deposits appear as water-clear vacuoles and are PAS positive staining. Accumulation occurs due high glucose concentrations. Such accumulations are common in:

• Poorly controlled diabetes mellitus
• Found in renal proximal tubules, the liver and cardiac myocytes
• Glycogen storage diseases (aka Glycogenoses)

Glycogenoses (Glycogen storage diseases) are an inherited genetic disorder that results in enzymatic defect in synthesis and/or breakdown of glycogen (remember, glycogen is the bodies store for glucose). These conditions are Autosomal recessive, and result in excessive accumulation of glycogen in the tissues.

H&E, liver in glycogen storage disease: hepatocytes distended by glycogen look clear and pale, with sharp cell borders like plant cells (portal tract in the middle). Glycogen is confirmed with PAS.

Image: “Glycogen storage disease in liver - high mag” by Nephron, CC BY-SA 3.0, via Wikimedia Commons.

There are various forms of glycogenosis, based on the specific enzyme deficiency, based on pathophysiology, we can break Glycogenoses into three categories:

1. 1. Hepatic type
2. a. Deficiency of the hepatic enzyme involved in glycogen metabolism
3. b. Leads to enlargement of liver due to high glycogen and hypoglycemia due to lack of free glucose
4. c. Von Gierke’s disease is an example
5. 2. Myopathic type
6. a. Deficiency of the skeletal muscle enzymes involved in glycolysis are deficient
7. b. Leads to muscle weakness
8. c. E.g. McArdle’s disease
9. 3. Generalised glycogenosis
10. a. Any other enzymopathy related to glucose metabolism
11. b. Example is Pompe disease

Remember: one classic disease for each type:

• Von Gierke (type I) – glucose-6-phosphatase: big liver and kidneys, severe fasting hypoglycaemia.
• McArdle (type V) – muscle phosphorylase: cramps after exercise without the normal rise in blood lactate.
• Pompe (type II) – lysosomal acid maltase: glycogen in all organs, massive cardiomegaly, early death from cardiorespiratory failure (infantile form).