Introduction
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 |
Mild elevation, High | ||||
ENO3
| Glycogen storage disease type XIII | Normal | AR | Aerobic and anaerobic exercise, symptom onset within minutes |
High | ||||
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 |
High | ||||
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
| AR | |||
Disorders of fatty acid metabolism:
| ||||
ACADVL
| Deficiency of very-long-chain acyl-CoA dehydrogenase | Normal | AR | Fasting, prolonged exercise, cold, infections, fever |
High | ||||
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
| ||||
Mitochondrial disorders
| ||||
COI (MTCO1)
| Mitochondrial disorder | Normal | Maternal inheritance | Prolonged or repetitive exercise |
COII
| Mitochondrial disorder | Normal | Maternal inheritance | Exercise |
(MTCO2)
| ||||
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] |
High | ||||
HADHA
| Mitochondrial Trifunctional Protein Deficiency | Normal | AR | Strenuous physical activity |
HADHB
| ||||
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 | |
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 |
Metabolic disorders
Disorders of glycogen metabolism
Muscle Glycogen Phosphorylase (PYGM)
Phosphofructokinase, Muscle Type (PFKM)
Aldolase A, Fructose-bisphosphate (ALDOA)
Beta Enolase 3 (ENO3)
Phosphoglycerate Mutase 2 (PGAM2)
Phosphoglycerate Kinase 1 (PGK1)
Phosphoglucomutase 1 (PGM1)
Phosphorylase Kinase, Muscle, Alpha-1 Subunit (PHKA1), Phosphorylase Kinase, Liver, Alpha-2 Subunit (PHKA2), Phosphorylase Kinase, Beta Subunit (PHKB), Phosphorylase Kinase, Testis/Liver, Gamma-2 (PHKG2)
Disorders of fatty acid metabolism
ACYL-CoA Dehydrogenase, Very long-chain (ACADVL)
Carnitine Palmitoyltransferase II (CPT2)
Electron Transfer Flavoprotein, Alpha Polypeptide (ETFA), Electron Transfer Flavoprotein, Beta Polypeptide (EFTB), Electron Transfer Flavoprotein Dehydrogenase (ETFDH)
Mitochondrial disorders
Disorders of intramuscular calcium release and excitation-contraction coupling
Ryanodine Receptor 1 (RYR1)
Muscular dystrophies
Miscellaneous
LPIN1
SIL1, S. Cerevisiae, Homolog Of (SIL1)
tRNA Splicing Endonuclease 54, S. Cerevisiae, Homolog Of (TSEN54)
Genetic Polymorphisms and association with RM
Gene
|
Exercise related symptoms
|
rs# (dbSNP)
|
Comments
|
Ref
|
---|---|---|---|---|
ACE
| Increased CK levels following eccentric exercise | rs4340 | Dose dependent increase of CK (II higher than ID) | [102] |
No association | rs4340 | - | [101] | |
No association | rs4340 | - | [100] | |
ACTN3
| Exertion rhabdomyolysis | rs1815739 | TT genotype | [100] |
No association with CK/Mb changes | rs1815739 | TT genotype – lower baseline CK | [104] | |
CCL2
| Exercise-induced skeletal muscle damage following maximal eccentric exercise | rs3917878, rs13900, rs1024611, rs1860189 | rs3917878 – high CK response (women) and attenuated strength recovery (men) rs13900, rs1024611 and rs1860189 - abnormal preexercise CK level (women) | [106] |
CCR2
| Exercise-induced skeletal muscle damage following maximal eccentric exercise | rs3918358, rs768539, rs1799865, | rs3918358 – slower strength recovery (women) rs1799865 – soreness rs1799865 – abnormal preexercise CK level (women) rs768539 and rs3918358 – preexercise strength (men) | [106] |
CKMM
| Exertion rhabdomyolysis | rs1803285 | GG genotype | [100] |
Increased CK following exertion | rs1803285 | AA genotype | [101] | |
IGF-II
| Muscle damage following maximal isotonic eccentric contractions | rs3213221, rs680, rs7924316, rs2132570 | Strength loss, soreness and high CK (Muscle damage indicators) | [105] |
IL6
| Increased CK levels following maximal eccentric exercise | rs13447445 | Dose dependent increase of CK (CC higher than CG genotypes) | [107] |
No association | rs13447445 | - | [100] | |
MYLK
| No association | rs2700352 | - | [100] |
Muscle damage following maximal eccentric exercise | rs2700352, rs28497577 | GG has greater increase in CK and myoglobin following exercise, higher baseline strength AC greater increase CK following exercise, postexercise strength loss (no AA data) | [104] | |
Exertion rhabdomyolysis | rs28497577 | AC or AA | [100] | |
TNFA
| Increased CK levels following maximal eccentric exercise | rs361525 | Mild association | [107] |