STEPTRACKERBIOCHEMISTRY + PEDIATRICS + PATHOLOGY | CARBOHYDRATE METABOLISM | HIGH-YIELD REVIEW

Glycogen & Glycogen Storage Diseases

How liver and muscle build and break glycogen — and the four storage diseases you must separate by organ, sugar and lactate.

FOCUS ON
"Very Poor Carbohydrate Metabolism" = types I–V: I von Gierke (glucose-6-phosphatase; severe fasting hypoglycemia, ↑ lactate, ↑ TG, ↑ uric acid, big liver and kidneys), II Pompe (lysosomal acid α-glucosidase; cardiomegaly, hypotonia — "Pompe trashes the Pump"), III Cori (debranching enzyme; milder, normal lactate), V McArdle (muscle phosphorylase; exercise cramps, myoglobinuria, no lactate rise, second-wind). All AR.
ENZYME · DISEASE
DEFECT
FEATURES
CLUE · TREATMENT
Glycogen synthase
Adds glucose (from UDP-glucose) in α-1,4 links; branching enzyme adds α-1,6 branches
Activated by insulin; inhibited by glucagon/epinephrine
Rate-limiting for synthesis
Glycogen phosphorylase
Removes glucose-1-P from α-1,4 links (B6 cofactor) until 4 residues from a branch
Activated by glucagon (liver), epinephrine, AMP and Ca²⁺ (muscle)
Rate-limiting for breakdown
Debranching enzyme
4-α-D-glucanotransferase moves 3 residues; α-1,6-glucosidase frees the branch glucose
—
Limit dextrin accumulates if absent
Type I — von Gierke
Glucose-6-phosphatase (Ia) or G6P translocase (Ib, + neutropenia)
Severe fasting hypoglycemia, seizures, lactic acidosis, ↑ triglycerides, ↑ uric acid (gout), hepatomegaly, renomegaly, doll face
Frequent cornstarch feeds · avoid fructose/galactose · no glucagon response
Type II — Pompe
Lysosomal acid α-1,4-glucosidase (acid maltase)
Infantile: cardiomegaly, hypertrophic cardiomyopathy, hypotonia, macroglossia, early death; normal blood glucose
Lysosomal storage disease too · enzyme replacement (alglucosidase)
Type III — Cori
Debranching enzyme (α-1,6-glucosidase)
Milder hypoglycemia, hepatomegaly, myopathy; normal lactate; abnormal short-branched glycogen (limit dextrin)
Gluconeogenesis intact → milder than von Gierke
Type V — McArdle
Muscle glycogen phosphorylase (myophosphorylase)
Exercise intolerance, painful cramps, myoglobinuria (red urine, renal risk), ↑ CK, flat venous lactate on ischemic forearm test; "second wind"
Blood glucose normal (liver fine) · pre-exercise sucrose
Type VI — Hers
Hepatic glycogen phosphorylase
Mild hypoglycemia, hepatomegaly
Benign-ish
Andersen (type IV)
Branching enzyme
Abnormal long-chain glycogen → cirrhosis in infancy, myopathy
Rare
Liver vs muscle glycogen
Liver: maintains blood glucose (has G6Pase) · muscle: fuels itself only
Liver diseases → hypoglycemia; muscle diseases → cramps, weakness
Sort GSDs by organ first

Mechanism — glycogen breakdown

Glucagon (liver) / epinephrine (muscle)
→
cAMP → PKA → phosphorylase kinase
→
Glycogen phosphorylaseα-1,4 → glucose-1-P
→
Debranching enzymeFrees branches
→
G6P → glucose (liver only)

Muscle stops at G6P and uses it for glycolysis; lysosomes also digest a little glycogen (acid maltase — Pompe).

Four GSDs side by side

TYPE
GLUCOSE
LACTATE
MAIN ORGAN
I von Gierke
Very low
↑
Liver, kidney
II Pompe
Normal
Normal
Heart, muscle
III Cori
Low
Normal
Liver, muscle
V McArdle
Normal
No rise with exercise
Skeletal muscle

How it's tested

COMMON CONFUSIONVon Gierke vs Cori: both hepatomegaly + hypoglycemia; lactate is high only in von Gierke (G6P backs up into glycolysis).
THE TRAPPompe is a glycogen storage disease AND a lysosomal storage disease — glucose is normal, the heart is the problem.
YOUR APPROACHLiver (hypoglycemia) vs muscle (cramps) vs heart (cardiomegaly) → lactate level → specific enzyme.

If you see… think…

Infant with severe fasting hypoglycemia, lactic acidosis, big liver and kidneys → von Gierke (G6Pase)
Glycogen storage disease with gout and hyperlipidemia → von Gierke
Floppy infant with massive cardiomegaly, normal glucose → Pompe (acid maltase)
Hypoglycemia + hepatomegaly with normal lactate, limit dextrin → Cori (debranching)
Young adult with exercise cramps and red urine → McArdle (myophosphorylase)
No rise in lactate after ischemic forearm exercise → McArdle
GSD with neutropenia and recurrent infections → von Gierke type Ib
Treatment of von Gierke between meals → uncooked cornstarch
Enzyme replacement for a glycogen storage disease → Pompe
Cofactor of glycogen phosphorylase → pyridoxal phosphate (B6)