Table 1

Genetic disorders with increased risk (or lowered threshold) of exertional rhabdomyolysis

Symptoms onset: timely relation to exerciseType of exercise that may trigger RMDiagnostic clue*
Muscle fuels and ATP production
Disorders of glycogen metabolism
PYGM, PFKM, ENO3, PGAM2, PGK1, PGM1, PHKA1, PHKB
Few minutesAerobic 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 exerciseSymptoms 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
UnspecifiedProlonged 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 daysUnaccustomed exercise
Strenuous exercise
Exercise performed in combination with different triggers
Associated triggers (eg, hot weather), muscle hypertrophy, heat intolerance
Caveolinopathy CAV369Minutes to a few hoursExercise (unspecified)
Moderate intensity of endurance activity
Muscle rippling, PIRCs
Other structural myopathies
LGMD's
Sarcoglycanopathies, FKRP, DYSF70 71
UnspecifiedProlonged intense exercise
Moderate physical activity
Weightlifting
Unspecified
Dystrophinopathies (DMD, BMD or carrier state)57
DMD
UnspecifiedUnspecifiedIncreased baseline CK level, gender (DMD)
Other genetic conditions
Sickle cell traitDuring or immediately after exercise. A few hours following exercise.Combination of intense sustained exercise in association with sickle cell trait-related RM triggersAfrican 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.