NGS Rhabdomyolysis and Metabolic Myopathies Panel
|Disorders||Fatty acid oxidation disorders
Glycogen metabolism disorders
Malignant hyperthermia susceptibility
This panel consists of 47 genes that may be considered in the evaluation of patients with elevated CK levels, muscle cramping and weakness, myoglobinuria, or rhabdomyolysis. The conditions included range in severity and include various forms of disorders of fatty acid and glycogen metabolism, mitochondrial disorders, muscular dystrophies, and others. Myopathic disorders presenting with leg cramps carry a risk of either rhabdomyolysis or progressive muscle weakness and can easily be missed Rhabdomyolysis results from the breakdown of skeletal muscle that may occur from a combination of environmental and genetic factors, and episodes can be triggered by a variety of factors. Initial symptoms may occur following strenuous exercise, infections, fasting, temperature extremes, or exposure to drugs or alcohol, and the signs of rhabdomyolysis include myoglobinuria, or darkened and discolored urine, that could lead to renal failure if left untreated. Some disorders that place individuals at risk for rhabdomyolysis are characterized by a "second-wind" phenomenon where initial exercise intolerance is overcome after a short period of rest. Susceptibility to malignant hyperthermia may also present with evidence of muscle breakdown after exposure to certain anesthetics, and this condition can be life-threatening without prompt recognition and treatment.
Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.
The current design of the rhabdomyolysis and metabolic myopathies panel covers the coding region for all 47 genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. All novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts.
We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution whole genome SNP microarray. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.
The following can also be ordered as individual sequencing tests:
Effective January 1, 2017, all NGS panels are performed on an exome backbone with the potential for reflex to whole exome sequencing at a reduced cost. Please contact the laboratory to discuss the requirements for exome sequencing.
|Specimen Requirements||5 to 10 ml of peripheral blood collected in an EDTA (lavender top) Vacutainer tube is preferred. The minimal blood needed for reliable DNA isolation is 3 ml.|
|Transport||The specimen should be kept at room temperature and delivered via overnight shipping. FedEx is preferred. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.|
|Turnaround time||8-10 weeks|
If the pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies. Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.
Insurance billing is available for this test. The Insurance Billing Form is required along with copies of the authorization or letter of agreement from the insurance company.