Rhabdomyolysis is caused by the breakdown of muscle leading to an increase in serum and urine myoglobin, and creatine kinase levels (CK previously referred to as CPK). Rhabdomyolysis can be caused by a number of conditions including excessive exercise, drugs, congenital muscular dystrophies and inborn errors of metabolism. The most common inborn errors of metabolism include fatty acid oxidation disorders, glycogen storage diseases, and mitochondrial disorders.
1. Renata Siciliani Scalco, et al. Orphanet J Rare Dis. May 2015; 10-51.
This test is indicated for:
- Individuals with recurrent episodes of rhabdomyolysis.
- Individuals with an unexplained rise in CPK.
Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient's genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not meant to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient's gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.
Copy Number Analysis: Comparative analysis of the NGS read depth (coverage) of the targeted regions of genes on this panel was performed to detect copy number variants (CNV). The accuracy of the detected variants is highly dependent on the size of the event, the sequence context and the coverage obtained for the targeted region. Due to these variables and limitations a minimum validated CNV size cannot be determined; however, single exon deletions and duplications are expected to be below the detection limit of this analysis.
Next Generation Sequencing: Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient's clinical/biochemical phenotype.
Analytical sensitivity for sequence variant detection is ~99%.
Copy Number Analysis: The sensitivity and specificity of this method for CNV detection is highly dependent on the size of the event, sequence context and depth of coverage for the region involved. The assay is highly sensitive for CNVs of 500 base pairs or larger and those containing at least 3 exons. Smaller (< 500 base pairs) CNVs and those that involving only 1 or 2 exons may or may not be detected depending on the sequence context, size of exon(s) involved and depth of coverage.
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Orangene™ Saliva Collection Kit used according to manufacturer instructions. Please contact EGL for a Saliva Collection Kit for patients that cannot provide a blood sample.
Please indicate any medications or dietary changes on the test requisition.
- Acylcarnitine Profile
- Carnitine Concentration Profile
- Organic Acids Quantative Analysis
- Coenzyme Q10 Profile, plasma
- Urine Amino Acids
- Urine Carnitine Profile
- Myophosphorylase Deficiency (McArdle Disease): PYGM Mutation Panel Test, Full Gene Sequencing and Deletion/Duplication Analysis
- Adenosine Monophosphate Deaminase 1 Deficiency: AMPD1 Mutation Panel Test and Full Gene Sequencing
- Medium Chain Acyl Co-A Dehydrogenase Deficiency: ACADM Mutation Panel Test, Full Gene Sequencing, and Deletion/Duplication Analysis
- CPT2: CPT2 Full Gene Sequencing and Deletion/Duplication Analysis
- Glutaric Aciduria Type 2 (GA II): ETFA, ETFB Full Gene Sequencing and Deletion/Duplication Analysis