McArdle’s Disease (Myophosphorylase Deficiency)

Pathophysiology

1) glycogen storage disease with increased accumulation of glycogen in skeletal muscles 2) cause is defect in muscle phophorylase 3) not progressive and only slightly debilitating

Signs and Symptoms

1) onset of symptoms in late teens/early adulthood 2) muscle spasms, pain, fatigue, and cramps on exercise or exertion (worse if activity is brief and intense such as running up stairs) 3) if patient rests after exertion, a second wind effect takes place and symptoms lessen

Characteristic Test Findings

Laboratory – 1) lack of lactate production (used as a diagnostic test) 2) myoglobinuria 3) increased CK (may be 100 times normal) 4) increases serum ammonia 5) diagnosis is also made by histochemical reaction for myophosphorylase, gene studies of DNA, and biochemical assay of enzyme activity in muscle

Histology/Gross Pathology

1) myofiber necrosis is evident on strenuous exercise 2) slight accumulation of glycogen particles is visible in sarcoplasm

Associated Conditions

renal failure if severe myoglobinuria occurs and is not treated

Biochemistry

1) muscle phophorylase causes release of glucose-1-phosphate from glycogen 2) if muscle phophorylase is absent the 1.4 glycosidic chains cannot be cleaved

Inheritance/Epidemiology

1) autosomal recessive 2) cause is a nonsense gene mutation on chromosome 11q13, which causes arginine to be changed to a stop codon 3) more common in men

Treatment

1) symptoms do not occur if there is no muscle exercise 2) if myoglobinuria occurs, patient needs hydration and vigorous diuresis 3) exercise tolerance can be improved with graduated aerobic activity 4) controversy exists as to whether diet modification (high protein diet, glucose ingestion before exercise) lessens symptoms

Tips for USMLE

if a 17 year old male experiences for the first time stabbing pain in his legs and arms when he is carrying furniture into his third-floor dorm room and then notices wine-colored urine, think McArdle’s