Symptoms onset: timely relation to exercise | Type of exercise that may trigger RM | Diagnostic clue* | |
---|---|---|---|
Muscle fuels and ATP production | |||
Disorders of glycogen metabolism PYGM, PFKM, ENO3, PGAM2, PGK1, PGM1, PHKA1, PHKB | Few minutes | Aerobic exercise Anaerobic exercise Strenuous exercise | Increased baseline CK level, vacuolar myopathy with glycogen accumulation (muscle biopsy), blunted increase in lactate in forearm exercise test (except: PHKA1, PHKB) PYGM: second-wind phenomenon PFKM: ‘out-of-wind phenomenon’, polyglucosan bodies (muscle biopsy) PGAM2: tubular aggregates (muscle biopsy) PGK1: central nervous system symptoms PGM1: multisystem features Haemolytic anaemia: PFKM, PGK1 |
Disorders of long-chain fatty acid metabolism ACADVL, CPT2, ETFA, ETFB, ETFDH, MTP | Later onset (Usually >45 min to hours) | Prolonged aerobic exercise | Symptoms are not triggered by isometric muscle contraction Abnormal fasting blood acylcarnitine profile Fasting and catabolic stress may trigger RM ETFA, ETFB, ETFDH: metabolic acidosis Peripheral neuropathy in MTP deficiency |
MMs COI (MTCO1), COII (MTCO2), COIII (MTCO3), FDX1 L, HADHA, HADHB, ISCU, MTCYB, mtDNA | Unspecified | Prolonged or repetitive exercise Strenuous exercise Unspecified | Multisystem features Abnormal muscle biopsy (ragged red fibres, COX-negative fibres) Autosomal recessive or maternal inheritance iron-sulfur cluster assembly enzyme: iron accumulation (muscle biopsy) RM is exceptional in MMs and FAO disorders should be excluded before considering an MM. |
Disorders of calcium homeostasis | |||
Calcium-influx disorders MHS KDS RYR1 | Hours to a few days | Unaccustomed exercise Strenuous exercise Exercise performed in combination with different triggers | Associated triggers (eg, hot weather), muscle hypertrophy, heat intolerance |
Caveolinopathy CAV369 | Minutes to a few hours | Exercise (unspecified) Moderate intensity of endurance activity | Muscle rippling, PIRCs |
Other structural myopathies | |||
LGMD's Sarcoglycanopathies, FKRP, DYSF70 71 | Unspecified | Prolonged intense exercise Moderate physical activity Weightlifting Unspecified | |
Dystrophinopathies (DMD, BMD or carrier state)57 DMD | Unspecified | Unspecified | Increased baseline CK level, gender (DMD) |
Other genetic conditions | |||
Sickle cell trait | During or immediately after exercise. A few hours following exercise. | Combination of intense sustained exercise in association with sickle cell trait-related RM triggers | African descent Risk of sudden death |
Unspecified: symptoms may occur during or after exertion; little information about type of physical activilty is available in literature.
*The absence of a diagnostic clue does not exclude the diagnosis in some of the reported conditions.
BMD, Becker muscular dystrophy; CK, creatine kinase; COX, cytochrome c oxidase; DMD, Duchenne muscular dystrophy; KDS, King-Denborough syndrome; LGMDs, limb-girdle muscular dystrophies; MHS, malignant hyperthermia susceptibility; MM, mitochondrial myopathy; PIRCs, percussion-induced rapid muscle contractions; RM, rhabdomyolysis; RYR1, type 1 ryanodine receptor.