Correct Answer: B. McArdle disease
McArdle disease (glycogen storage disease type V) is caused by deficiency of the enzyme muscle phosphorylase, which catalyzes the first step of glycogenolysis in skeletal muscle—the breakdown of glycogen to glucose-1-phosphate. This enzyme defect is unique to muscle tissue; liver phosphorylase is intact.
The clinical presentation is pathognomonic: exercise-induced hypoglycemia and muscle cramps that resolve with rest. During exertion, muscles cannot mobilize glucose from their glycogen stores, leading to energy depletion and cramping. Systemic hypoglycemia occurs because the liver cannot compensate adequately (it relies on muscle-derived lactate for gluconeogenesis via the Cori cycle). The decreased serum lactate is the discriminating finding—lactate is normally produced by anaerobic muscle metabolism during exercise, but in McArdle disease, muscles cannot generate lactate because glycolysis cannot proceed without glucose-1-phosphate from glycogenolysis. This creates a "second wind" phenomenon: after 10–15 minutes of rest, alternative fuels (fatty acids, amino acids) mobilize, allowing symptoms to resolve.
Diagnosis is confirmed by absent or severely reduced muscle phosphorylase activity on muscle biopsy or genetic testing. Indian patients often present after school sports or play activities. Management includes avoiding strenuous exercise, frequent small meals, and oral glucose during episodes. Unlike other GSDs, McArdle disease does not cause hepatomegaly or liver dysfunction.
Why the other options are wrong
A. Hers disease — Hers disease (GSD VI) is caused by hepatic phosphorylase deficiency. It presents with hepatomegaly, mild fasting hypoglycemia, and growth retardation—not exercise-induced muscle cramps. Serum lactate is normal or elevated, not decreased. Muscle function is unaffected because muscle phosphorylase is intact. This is a trap for students who confuse phosphorylase deficiencies across tissues. C. Cori's disease — Cori disease (GSD III) involves debranching enzyme deficiency, causing hepatomegaly, fasting hypoglycemia, and hepatic dysfunction. Muscle involvement is mild and does not cause exercise-induced cramps. Lactate levels are typically elevated, not decreased. The clinical picture is dominated by liver disease, not muscle symptoms triggered by activity. D. Andersen disease — Andersen disease (GSD IV) is caused by branching enzyme deficiency, leading to abnormal glycogen accumulation, cirrhosis, hepatosplenomegaly, and early death (usually by age 5). It does not present with exercise-induced hypoglycemia or muscle cramps in older children. The severe hepatic phenotype and early mortality distinguish it from the benign muscle-limited presentation here.
High-Yield Facts
- McArdle disease = muscle phosphorylase deficiency (GSD V); presents with exercise-induced hypoglycemia, muscle cramps, and decreased serum lactate (pathognomonic).
- Second wind phenomenon: symptoms resolve after 10–15 minutes of rest as alternative fuels (fatty acids, amino acids) mobilize.
- No hepatomegaly in McArdle disease—liver phosphorylase is intact; liver function is normal.
- Hers disease (GSD VI) = hepatic phosphorylase deficiency; hepatomegaly and fasting hypoglycemia, NOT exercise-induced muscle symptoms.
- Cori disease (GSD III) = debranching enzyme deficiency; hepatomegaly dominates; mild muscle involvement.
- Andersen disease (GSD IV) = branching enzyme deficiency; severe cirrhosis and early death; no exercise-induced symptoms.
Mnemonics
McArdle = Muscle Phosphorylase McArdle disease = Muscle Phosphorylase deficiency. Remember: M–P. Exercise → no glucose from glycogen → cramps + hypoglycemia + LOW lactate (no anaerobic glycolysis). GSD Phosphorylase Deficiencies Hers (GSD VI) = Hepatic phosphorylase → hepatomegaly. McArdle (GSD V) = Muscle phosphorylase → muscle cramps. Different tissues, different presentations. Second Wind Phenomenon McArdle disease: exercise → cramps → rest 10–15 min → second wind (fatty acid oxidation kicks in). This is pathognomonic and resolves symptoms.
NBE Trap
NBE pairs "decreased lactate" with hypoglycemia to trap students who expect lactate to be elevated in all exercise states. In McArdle disease, the block occurs before lactate production (at glycogenolysis), so lactate is paradoxically low—the key discriminator.
Clinical Pearl
In Indian schools and sports settings, McArdle disease often goes undiagnosed until a child collapses during PT class or cricket. The key bedside clue is the second wind—parents report the child recovers completely after 15 minutes of rest, which is unique to McArdle and should trigger immediate serum lactate and muscle phosphorylase testing.
_Reference: Robbins & Cotran Pathologic Basis of Disease, Ch. 5 (Genetic Disorders); KD Tripathi Biochemistry, Ch. 8 (Carbohydrate Metabolism & GSDs)_