Glycogen Storage Diseases (GSD Types I – VI)
| Type & Name | Deficient Enzyme | Key Clinical Presentation & Diagnostics |
|---|---|---|
| Type I Von Gierke |
Glucose-6-Phosphatase | Severe fasting hypoglycemia, massive hepatomegaly, lactic acidosis, hyperuricemia (gout), and hyperlipidemia. Doll-like facies. Does NOT respond to glucagon. |
| Type II Pompe |
Lysosomal α(1→4)-Glucosidase (Acid Maltase) | Infantile hypertrophic cardiomegaly, profound hypotonia (“floppy baby”), and early death. Glycogen accumulation inside membrane-bound lysosomes. Blood glucose is normal. |
| Type III Cori |
Debranching Enzyme (α-1,6-glucosidase) | Milder fasting hypoglycemia, hepatomegaly. Accumulation of abnormal limit dextrins (short outer branches). Blood lactate levels are NORMAL; gluconeogenesis remains intact. |
| Type IV Andersen |
Branching Enzyme (α-1,4 → α-1,6 transglucosidase) | Infantile cirrhosis, massive hepatosplenomegaly, progressive hepatic failure. Accumulation of abnormal, unbranched long chains (polyglucosan bodies) that provoke an immune response. |
| Type V McArdle |
Skeletal Muscle Glycogen Phosphorylase | Muscle cramps and weakness during initial exercise, “second-wind” phenomenon (due to fatty acid utilization). Severe exertion triggers rhabdomyolysis and myoglobinuria (burgundy urine). Normal blood glucose. |
| Type VI Hers |
Hepatic Glycogen Phosphorylase | Mild fasting hypoglycemia, hepatomegaly. Often benign and discovered incidentally during childhood workup, it improves with age. |
High-Yield Diagnostic Yields:
- The Lactate Differential Trap: Type I (Von Gierke) and Type III (Cori) present with identical fasting hypoglycemia and hepatomegaly. Differentiate them solely by blood lactate: Type I has massive lactic acidosis, while Type III has normal lactate.
- Ischemic Forearm Exercise Test: Used to diagnose Type V (McArdle). Squeezing a dynamometer with a blood pressure cuff inflated leads to a normal rise in ammonia but zero rise in post-exercise blood lactate due to blocked glycogenolytic flux.
- “Pompe Trashes the Pump”: Type II (Pompe) is fundamentally a lysosomal storage disease affecting muscular structures, heavily destroying cardiac muscle walls, whereas standard hepatic variants primarily disrupt systemic glycemic stability.