Description
Rhabdomyolysis and metabolic muscle disorders inclusion criteria (29559)
- At least 2 of the criteria listed below: 
- Symptom triggers: Exercise, fasting, fever and heat 
- Variable CK with exacerbations >10x above basal value  
- Myoglobinuria (tea or coca cola coloured urine) 
- In patient treatment for acute rhabdomyolysis with or without acute renal failure  
- Muscle weakness is progressive 
- Usually muscle pain associated with atrophy and weakness 
- Malignant Hyperpyrexia syndrome 
- Neuroleptic Malignant syndrome 
- Acute compartment Syndrome  

Individuals with severe or syndromic disease should be recruited according to standard guidance, typically as trios. Disease status of apparently unaffected participants should be determined according to standard clinical practice to detect cryptic disease.  In other cases, unaffected individuals should not be recruited. Recruitment in such families should favour multiplex families over single isolated cases. These singleton recruits will not contribute to the overall singleton monitoring metrics applied to GMCs.

Rhabdomyolysis and metabolic muscle disorders exclusion criteria (29559)
- Non exercise related limb pain
- Muscle biopsy with histochemical enzyme or sarcolemmal protein deficiencies to indicate a diagnosis of GSDV, GSDVII or muscular dystrophy (Becker or LGMD)
- Abnormal fasting blood acyl carnitines and/or urine organic acids consistent with a known FAODD
- Confirmed viral induced myositis without myoglobinuria
- Prescribed (e.g. statin) or recreational drug triggers
- Severe trauma

Prior genetic testing guidance (29559)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Closing statement (29559)
These requirements will be kept under continual review during the main programme and may be subject to change.

4 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Ros Quinlivan (UCLH)

    Group: Other NHS organisation
    Workplace: Other clinical service

  • Richard Kirk (Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust)

    Group: GeCIP domain
    Workplace: NHS diagnostic lab

  • Sarah Leigh (Genomics England Curator)

    Group: Other
    Workplace: Other

55 genes

55 reviewed, 47 green

List Gene Reviews Mode of inheritance Details
55 genes
Green Green List (high evidence)
ACAD9
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Literature
Phenotypes
  • Mitochondrial complex I deficiency due to ACAD9 deficiency 611126
Green Green List (high evidence)
ACADM
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • Expert Review Green
Phenotypes
  • Rhabdomyolysis
  • Acyl-CoA dehydrogenase, medium chain, deficiency of 201450
Green Green List (high evidence)
ACADVL
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
Phenotypes
  • VLCAD deficiency 201475
Green Green List (high evidence)
AGL
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Glycogen storage disease IIIa 232400
  • Glycogen storage disease IIIb 232400
Green Green List (high evidence)
ALDOA
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
  • Expert Review Green
Phenotypes
  • Glycogen storage disease XII 611881
Green Green List (high evidence)
ANO5
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
Phenotypes
  • Miyoshi muscular dystrophy 3 613319
  • Muscular dystrophy, limb-girdle, type 2L 611307
Green Green List (high evidence)
CACNA1S
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • {Malignant hyperthermia susceptibility 5}, 601887
Green Green List (high evidence)
CAV3
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Muscular dystrophy, limb-girdle, type IC 607801
  • Myopathy, distal, Tateyama type 614321
  • Rippling muscle disease 606072
Green Green List (high evidence)
CPT2
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • CPT II deficiency, myopathic, stress-induced (exercise intolerance and rhabdomyolysis, late onset) 255110
Green Green List (high evidence)
DMD
2 reviews
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • Becker muscular dystrophy 300376
Tags
  • gene-therapy-trial
Green Green List (high evidence)
DYSF
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Expert Review Green
Phenotypes
  • Miyoshi muscular dystrophy 1 254130
  • Muscular dystrophy, limb-girdle, type 2B 253601
  • Myopathy, distal, with anterior tibial onset 606768
Green Green List (high evidence)
ENO3
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • UKGTN
  • Expert Review Green
Phenotypes
  • ?Glycogen storage disease XIII 612932
Green Green List (high evidence)
ETFA
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Literature
  • UKGTN
Phenotypes
  • Glutaric acidemia IIA 231680
Green Green List (high evidence)
ETFB
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Expert Review Green
  • Literature
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
Phenotypes
  • Glutaric acidemia IIB 231680
Green Green List (high evidence)
ETFDH
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • UKGTN
  • Expert Review Green
Phenotypes
  • Glutaric acidemia IIC 231680
Green Green List (high evidence)
FKRP
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • Expert Review Green
Phenotypes
  • Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5 607155
Green Green List (high evidence)
FKTN
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Fukuyama congenital muscular dystrophy
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 253800
Green Green List (high evidence)
GAA
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Glycogen storage disease II 232300
Green Green List (high evidence)
GBE1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Glycogen storage disease IV 232500
Green Green List (high evidence)
GYG1
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
  • UKGTN
Phenotypes
  • ?Glycogen storage disease XV 613507
  • Polyglucosan body myopathy 2 616199
Green Green List (high evidence)
GYS1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Glycogen storage disease 0, muscle 611556
Green Green List (high evidence)
HADHA
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Literature
  • UKGTN
Phenotypes
  • Trifunctional protein deficiency 609015
Green Green List (high evidence)
HADHB
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Trifunctional protein deficiency 609015
Green Green List (high evidence)
ISCU
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Myopathy with lactic acidosis, hereditary 255125
Tags
  • non-coding-known-pathogenic
Green Green List (high evidence)
LAMP2
1 review
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • Danon disease 300257
Green Green List (high evidence)
LDHA
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Literature
  • UKGTN
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Glycogen storage disease XI 612933
Green Green List (high evidence)
LPIN1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Myoglobinuria, acute recurrent, autosomal recessive 268200
Green Green List (high evidence)
PFKM
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Glycogen storage disease VII 232800
Green Green List (high evidence)
PGAM2
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Glycogen storage disease X 261670
Green Green List (high evidence)
PGK1
2 reviews
1 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
  • Emory Genetics Laboratory
Phenotypes
  • Phosphoglycerate kinase 1 deficiency 300653
Green Green List (high evidence)
PGM1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Literature
  • UKGTN
Phenotypes
  • Congenital disorder of glycosylation, type It 614921
Green Green List (high evidence)
PHKA1
2 reviews
1 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Literature
  • UKGTN
Phenotypes
  • Muscle glycogenosis 300559
Green Green List (high evidence)
PHKB
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
Phenotypes
  • Phosphorylase kinase deficiency of liver and muscle, autosomal recessive 261750
Green Green List (high evidence)
POLG
1 review
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Literature
Phenotypes
  • Mitochondrial DNA depletion syndrome 4A (Alpers type) 203700
  • Mitochondrial DNA depletion syndrome 4B (MNGIE type) 613662
  • Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) 607459
  • Progressive external ophthalmoplegia, autosomal dominant 1 157640
  • Progressive external ophthalmoplegia, autosomal recessive 1 258450
Green Green List (high evidence)
POLG2
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Literature
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 610131
Green Green List (high evidence)
PRKAG2
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • Cardiomyopathy, hypertrophic 6 600858
  • Glycogen storage disease of heart, lethal congenital 261740
  • Wolff-Parkinson-White syndrome 194200
Green Green List (high evidence)
PYGM
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • Glycogen storage disease V McArdle disease 232600 AR
Green Green List (high evidence)
RBCK1
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Expert Review Green
  • Expert Review
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Polyglucosan body myopathy 1 with or without immunodeficiency 615895
Green Green List (high evidence)
RRM2B
1 review
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Literature
Phenotypes
  • Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) 612075
  • Mitochondrial DNA depletion syndrome 8B (MNGIE type) 612075
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 613077
Green Green List (high evidence)
RYR1
1 review
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • {Malignant hyperthermia susceptibility 1}, 145600
  • Central core disease, 117000
  • Minicore myopathy with external ophthalmoplegia, 255320
  • Neuromuscular disease, congenital, with uniform type 1 fiber, 117000 King-Denborough syndrome, 145600
Green Green List (high evidence)
SIL1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • Marinesco-Sjogren syndrome 248800
Green Green List (high evidence)
SLC22A5
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Literature
  • UKGTN
Phenotypes
  • Carnitine deficiency, systemic primary 212140
Green Green List (high evidence)
SUCLA2
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) 612073
Green Green List (high evidence)
TK2
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) 612073
Green Green List (high evidence)
TSEN54
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Literature
Phenotypes
  • ?Pontocerebellar hypoplasia type 5 610204
  • Pontocerebellar hypoplasia type 2A 277470
  • Pontocerebellar hypoplasia type 4 225753
Green Green List (high evidence)
TSFM
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert Review
Phenotypes
  • Combined oxidative phosphorylation deficiency 3 610505
Green Green List (high evidence)
TYMP
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) 612073
Red Red List (low evidence)
AMPD1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • Rhabdomyolysis
  • Myopathy due to myoadenylate deaminase deficiency 615511
Red Red List (low evidence)
CPT1B
1 review
Not set
Sources
  • UKGTN
Red Red List (low evidence)
CYP2C8
2 reviews
1 green
Unknown
Sources
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Rhabdomyolysis, cerivastatin-induced
Tags
  • pharmacogenetics
Red Red List (low evidence)
FBP2
2 reviews
2 red
Not set
Sources
  • UKGTN
Red Red List (low evidence)
OBSCN
2 reviews
1 red
Unknown
Sources
  • Expert Review Red
Tags
  • watchlist
Red Red List (low evidence)
PHKG1
2 reviews
2 red
Not set
Sources
  • UKGTN
Red Red List (low evidence)
SLC22A12
2 reviews
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
Phenotypes
  • Hypouricemia, renal 220150
Red Red List (low evidence)
SLC2A9
2 reviews
1 red
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Red
Phenotypes
  • Hypouricemia, renal, 2 612076
  • {Uric acid concentration, serum, QTL 2} 612076

0 STRs

0 reviewed, 0 green

List STR Reviews Mode of inheritance Details
0 STRss

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