Bit · Biochem
Glycogen Storage Diseases (von Gierke, Pompe, Cori, McArdle)
Four classic glycogen storage diseases. Each is a different broken enzyme — and the clinical picture (liver vs heart vs muscle) tells you which one.
Mechanism
Glycogen is the body's short-term glucose reserve. Each disease breaks a different enzyme in the synthesis/breakdown pathway:
- Type I — von Gierke — glucose-6-phosphatase. Liver can't release glucose into blood. Severe fasting hypoglycemia, lactic acidosis, hyperuricemia, hyperlipidemia, doll-like facies, hepatomegaly.
- Type II — Pompe — lysosomal α-1,4-glucosidase (acid maltase). Glycogen accumulates in lysosomes throughout the body. Cardiomegaly, hypotonia, early death. 'Pompe trashes the Pump'.
- Type III — Cori — debranching enzyme. Milder von-Gierke-like picture with normal lactate (gluconeogenesis intact). Limit dextrins accumulate.
- Type V — McArdle — muscle glycogen phosphorylase. Muscle can't break down glycogen during exercise. Exercise intolerance, painful cramps, myoglobinuria. Classic second-wind phenomenon (after rest, fatty-acid oxidation takes over).
Differentiator Table
| Type | Name | Enzyme | Hallmark |
|---|---|---|---|
| I | Von Gierke | Glucose-6-phosphatase | Severe fasting hypoglycemia, lactic acidosis, hepatomegaly, doll facies |
| II | Pompe | Lysosomal α-1,4-glucosidase | Cardiomegaly + hypotonia + early death ('Pompe trashes the Pump') |
| III | Cori | Debranching enzyme | Milder von Gierke; NORMAL lactate; limit dextrins |
| V | McArdle | Muscle glycogen phosphorylase | Exercise intolerance, cramps, myoglobinuria, second-wind phenomenon |
The Pivot
Three questions:
- Cardiomegaly + hypotonia in infant? → Pompe.
- Fasting hypoglycemia + lactic acidosis + hepatomegaly? → von Gierke (lactic acidosis) or Cori (normal lactate).
- Exercise-induced cramps with red urine? → McArdle.
NBME-Style Stem
A 9-month-old boy is brought in for severe hypotonia and failure to thrive. Examination shows a macroglossia and massive cardiomegaly on chest x-ray. Echocardiography shows a thickened, hypocontractile left ventricle. Skin fibroblast assay reveals deficiency of acid α-1,4-glucosidase. Which of the following is the most likely diagnosis?
Concept Anchor
Four storage diseases, four broken steps, four organs: liver fails in von Gierke and Cori, heart fails in Pompe, muscle fails in McArdle. Match the organ to the enzyme.