Rhabdomyolysis: a genetic perspective

Scalco, Renata Siciliani; Gardiner, Alice R; Pitceathly, Robert DS; Zanoteli, Edmar; Becker, Jefferson; Holton, Janice L; Houlden, Henry; Jungbluth, Heinz; Quinlivan, Ros

doi:10.1186/s13023-015-0264-3

Orphanet Journal of Rare Diseases

Table 1 Inherited neuromuscular disorders associated with episodes of rhabdomyolysis

From: Rhabdomyolysis: a genetic perspective

Gene	Disease name	Baseline CK levels	Pattern of inheritance	Trigger for rhabdomyolysis
Disorders of glycogen metabolism
*PYGM*	Glycogen storage disease type V, McArdle disease	High	AR	Aerobic and anaerobic exercise, symptom onset within minutes
PFKM	Glycogen storage disease type VII, Tarui’s disease	High	AR	Aerobic and anaerobic exercise, symptom onset within minutes
ALDOA	Glycogen storage disease type XII	Normal	AR	Febrile illness, infection
ALDOA	Glycogen storage disease type XII	Mild elevation, High	AR	Febrile illness, infection
ENO3	Glycogen storage disease type XIII	Normal	AR	Aerobic and anaerobic exercise, symptom onset within minutes
ENO3	Glycogen storage disease type XIII	High	AR
PGAM2	Glycogen storage disease type X	High	AR	Aerobic and anaerobic exercise, symptom onset within minutes
PGK1	Phosphoglycerate kinase 1 deficiency	Normal	X-linked	Aerobic and anaerobic exercise, symptom onset within minutes
PGK1	Phosphoglycerate kinase 1 deficiency	High	X-linked
PGM1	Glycogen storage disease type XIV	High	AR	Aerobic and anaerobic exercise, symptom onset within minutes, general anaesthesia
PHKA1	Glycogen storage disease type IX	?	X-linked	Aerobic and anaerobic exercise, symptom onset within minutes
PHKB	Glycogen storage disease type IX	?	AR
Disorders of fatty acid metabolism:
*ACADVL*	Deficiency of very-long-chain acyl-CoA dehydrogenase	Normal	AR	Fasting, prolonged exercise, cold, infections, fever
*ACADVL*	Deficiency of very-long-chain acyl-CoA dehydrogenase	High	AR	Fasting, prolonged exercise, cold, infections, fever
*CPT2*	Carnitine palmitoyl-transferase deficiency	Normal	AR	Prolonged exercise, fasting, fever, infection, high fat intake, cold exposure, heat, emotional stress, drugs
ETFA	Glutaric aciduria Type II	Normal	AR	Physical exercise, fasting, irregular diet or infection
ETFB	Multiple acyl-coenzyme A dehydrogenase deficiency	Mildly to moderately elevated
ETFDH	Multiple acyl-coenzyme A dehydrogenase deficiency	Mildly to moderately elevated
Mitochondrial disorders
COI (MTCO1)	Mitochondrial disorder	Normal	Maternal inheritance	Prolonged or repetitive exercise
COII	Mitochondrial disorder	Normal	Maternal inheritance	Exercise
(MTCO2)	Mitochondrial disorder	Normal	Maternal inheritance	Exercise
COIII (MTCO3)	Mitochondrial disorder	Normal	Maternal inheritance	Prolonged exercise, viral illness, unknown cause
DGUOK	Mitochondrial disorder	?	AR	Viral illness
FDX1L	Mitochondrial disorder	Normal	AR	? After exercise [114]
FDX1L	Mitochondrial disorder	High	AR	? After exercise [114]
HADHA	Mitochondrial Trifunctional Protein Deficiency	Normal	AR	Strenuous physical activity
HADHB	Mitochondrial Trifunctional Protein Deficiency	Normal	AR	Strenuous physical activity
ISCU	Iron–sulphur cluster deficiency myopathy (Mitochondrial disorder)	?	AR	Exercise
MTCYB	Mitochondrial disorder	Normal	?Sporadic mutations [64]	Exercise
POLG1	1 case report of rhabdomyolysis in association with PIS [73]		AD, AR	PIS
Disorders of intramuscular calcium release and excitation-contraction coupling
*RYR1*	Malignant hyperthermia-susceptibility, Exertional rhabdomyolysis, Congenital myopathy	Normal or mildly to moderately elevated (usually <1000 IU/L)	AD, AR	Heat, infection, alcohol, drugs, anaesthetic (MHS) and exercise
Muscular dystrophies
ANO5	Anoctaminopathy-5	High	AR	Unprovoked – no trigger has been identified
*DMD*	Duchenne muscular dystrophy, Becker muscular dystrophy	High	X-linked	Exercise, anaesthetic drugs
DYSF	LGMD2B, Miyoshi myopathy	High	AR	Exercise
FKTN	Fukuyama congenital muscular dystrophy	High	AR	One case following the use of halothane and succinylcholine [89,90]
*FKRP*	LGMD2I	High	AR	Exercise [82]
Miscellaneous
*LPIN1*	Phosphatidic acid phosphatase deficiency	Normal, High	AR	Febrile illness, anaesthesia and fasting.
SIL1	Marinesco-Sjogren syndrome	Normal, High	AR	Febrile infection
TSEN54	Pontocerebellar hypoplasia type 2	Normal, High	AR	Hyperthermia

The table above summarises genes, disease name, baseline serum CK levels (between acute episodes of rhabdomyolysis), pattern of inheritance and triggers for rhabdomyolysis. Genes commonly associated with rhabdomyolysis episodes are indicated in bold.
CK: creatine kinase; AR: autosomal recessive; AD: autosomal dominant; MHS: malignant hyperthermia susceptibility; PIS: propofol infusion syndrome; LGMD: limb-girdle muscular dystrophy (2B and 2I).

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ISSN: 1750-1172

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