Glycogen Storage Diseases

Question 1

Debranching enzyme deficiency (Cori disease)

Answer 1

• presents in infancy or childhood with both liver and muscle involvement.
• Symptoms include hypoglycemia, hepatomegaly, and ketoacidosis
• Muscle weakness and hypotonia help to distinguish the condition from other glycogen storage diseases with hepatic involvement (eg, von Gierke, Hers)
• Hepatic fibrosis is common, but fatty infiltration is not usually seen
• key distinguishing feature is cytosolic accumulation of glycogen with abnormally short outer chains (limit dextrins).
• During glycogenolysis, glycogen phosphorylase shortens glycogen chains by cleaving α-1,4-glycosidic linkages between glucose residues, liberating glucose-1-phosphate in the process
• occurs until 4 residues remain before a branch point (the limit dextrin). At this point, debranching enzyme performs 2 enzymatic functions:
  1. Glucosyltransferase cleaves the outer 3 residues of the 4 glucose residues left by glycogen phosphorylase and transfers them to a nearby branch
  2. α-1,6-glucosidase removes the single remaining branch residue, producing free glucose and a linear glycogen chain that can be further shortened by glycogen phosphorylase

Question 2

Acid maltase deficiency (Pompe disease)

Answer 2

Small amounts of glycogen are broken down by the lysosomal enzyme acid maltase (has both α-1,4- and α-1,6-glucosidase activity).
- cardiomegaly, severe generalized hypotonia, and lysosomal glycogen accumulation (hypoglycemia is not seen).

Question 3

Glucose-6-phosphatase deficiency (von Gierke disease)

Answer 3

• affects mainly the liver and kidney, as the enzyme is not expressed in significant quantities in muscle tissue
• Major symptoms include hypoglycemia, lactic acidosis, hyperlipidemia, and hyperuricemia
• Hepatic steatosis is a cardinal manifestation of the disorder.

Question 4

Liver glycogen phosphorylase deficiency (Hers disease) does not affect skeletal muscles and would show an excess of normally structured glycogen (not limit dextrins) on liver biopsy.

Answer 4

presents in early childhood with mild hypoglycemia, ketosis, and hepatomegaly.

• does not affect skeletal muscles and would show an excess of normally structured glycogen (not limit dextrins) on liver biopsy.
• does not affect skeletal muscles and would show an excess of normally structured glycogen (not limit dextrins) on liver biopsy.

Question 5

Muscle glycogen phosphorylase deficiency causes McArdle disease

Answer 5

Blood lactate is often very low after exercise, and muscle biopsy shows an excess of normally structured glycogen.

Question 6

Pyruvate kinase deficiency

Answer 6

chronic hemolytic anemia as glycolysis is the main source of energy for erythrocytes.

• Pyruvate kinase converts phosphoenolpyruvate to pyruvate during glycolysis.