Rhabdomyolysis is a symptom that can have many causes, both acquired and genetic. Inherited metabolic myopathies are a significant cause, but with a wide range of causes including defects of glycogen storage, lipid metabolism and skeletal muscle channelopathies, as well as muscular dystrophies and mitochondrial disease. Exercise intolerance, muscle pain and weakness, and myoglobinuria are common symptoms that make a specific diagnosis very challenging due to the diversity of conditions.
Indications for Testing
Diagnostic testing to investigate a clinical/biochemical diagnosis of metabolic myopathy/rhabdomyolysis.
Testing in relatives of an affected individual for clinical management and genetic counselling. These referrals require that a pathogenic mutation has been identified in the index case.
Test sensitivity is >99% and test specificity is >99% compared to Sanger sequencing.
Clinical sensitivity is limited by the diversity of causes, including mitochondrial/respiratory chain defects which are not included in the panel. Sensitivity can be improved by use of a diagnostic algorithm e.g. Quinlivan and Jungbluth (2012) Dev Med Child Neurol 54:886-891.
Next generation sequencing of 30 genes associated with metabolic myopathies/rhabdomyolysis, including muscle glycogen storage diseases, fatty acid oxidation disorders, and RYR1-related myopathies:
ACADVL, AGL, ALDOA, CAV3, CPT1B, CPT2, ENO3, ETFA, ETFB, ETFDH, FBP2, GAA, GBE1, GYG1, GYS1, HADHA, HADHB, ISCU, LDHA, LPIN1, PFKM, PGAM2, PGK1, PGM1, PHKA1, PHKG1, PYGM, RBCK1, RYR1, SLC22A5
Venous blood (2-5ml K-EDTA, not to be frozen prior to or during transport)
Genomic DNA (minimum 5μg)
Specimen containers and referral forms must be labelled with at least two corresponding unique identifiers.
Approximately 12-16 weeks (60-80 working days) from receipt of sample. A priority service may be available for urgent referrals at an additional cost, please contact the laboratory for further information.
Referrals must generally be made from the Clinical Genetics services or appropriate clinical specialist. Please contact the laboratory if this is not possible. It is assumed that informed consent for genetic testing has been obtained from the patient or their parent/guardian and that the implications of a positive result for other family members have been discussed.
Metabolic Myopathies Rhabdomyolysis Diagnostic Test