Metabolic Myopathy and Rhabdomyolysis Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: ME1401

The Blueprint Genetics Metabolic Myopathy and Rhabdomyolysis Panel is a 40 gene test for genetic diagnostics of patients with clinical suspicion of glycogen storage disease, lipid storage disorder, metabolic myopathies or rhabdomyolysis.

Medical conditions associated with rhabdomyolysis are inherited via autosomal recessive, autosomal dominant and X-linked manner. Associated disorders are very different in types and causes. Disorders of glycogen metabolism and fatty acid metabolism are typically inherited in autosomal recessive manner. This Panel in included in the Comprehensive Metabolism Panel.

About Metabolic Myopathy and Rhabdomyolysis

Rhabdomyolysis is a medical condition in which damaged striated skeletal muscles break down easily and rapidly. Some end products of this lysis, such as myoglobin, are toxic to kidneys and may cause acute renal failure. Symptoms include muscle pain and vomiting. Common and important causes of rhabdomyolysis include several common situations, such as drugs and toxins, infections, hyperthermia, strong physical exercise and car accidents, earthquakes and bombings. However, recurrent rhabdomyolysis is often genetic in nature. The genetic causes for rhabdomyolysis include metabolic myopathy, disorders of intramuscular calcium release, mitochondrial disorders and muscular dystrophies. Metabolic myopathies are a group of genetic muscular diseases resulting from defective metabolism affecting primarily muscles. These myopathies are typically subdivided into three categories: i) glycogen storage diseases, ii) lipid storage diseases and iii) disorders of purine metabolism, all of which are associated with specific enzymatic defetcs that prevent adequate energy and ATP levels for muscle cells. This Panel includes comprehensively genes associated with all these medical conditions that can cause rhabdomyolysis of genegic origin. The prevalence of rhabdomyolysis is not known.

Availability

Results in 3-4 weeks.

Genes in the Metabolic Myopathy and Rhabdomyolysis Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ACAD9Acyl-CoA dehydrogenase family, deficiencyAR2140
ACADLLong chain acyl-CoA dehydrogenase deficiencyAD/AR2
ACADMAcyl-CoA dehydrogenase, medium chain, deficiencyAR59163
ACADVLAcyl-CoA dehydrogenase, very long chain, deficiencyAR53260
AGLGlycogen storage diseaseAR37237
ALDOAGlycogen storage diseaseAR28
C10ORF2Perrault syndrome, Mitochondrial DNA depletion syndromeAR31
CAV3Creatine phosphokinase, elevated serum, Hypertrophic cardiomyopathy (HCM), Long QT syndromeAD/Digenic2347
CPT1BCarnitine palmitoyltransferase deficiencyAD3
CPT2Carnitine palmitoyltransferase II deficiencyAR36102
ENO3Glycogen storage diseaseAR24
ETFAGlutaric aciduria, Multiple acyl-CoA dehydrogenase deficiencyAR728
ETFBGlutaric aciduria, Multiple acyl-CoA dehydrogenase deficiencyAR713
ETFDHGlutaric aciduria, Multiple acyl-CoA dehydrogenase deficiencyAR36168
GAAGlycogen storage diseaseAR79503
GBE1Glycogen storage diseaseAR2569
GYG1Glycogen storage diseaseAR710
GYS1Glycogen storage diseaseAR26
HADHATrifunctional protein deficiency, Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiencyAR2367
HADHBTrifunctional protein deficiencyAR1055
ISCUMyopathy with lactic acidosisAR32
LDHAGlycogen storage diseaseAR18
LPIN1Myoglobinuria, acute, recurrentAR629
OPA1Glaucoma, normal tensionAD67357
OPA3Optic atrophy, 3-methylglutaconic aciduriaAD/AR712
PFKMGlycogen storage diseaseAR1026
PGAM2Glycogen storage diseaseAR39
PGK1Phosphoglycerate kinase 1 deficiencyXL1426
PGM1Congenital disorder of glycosylationAR924
PHKA1Glycogen storage diseaseXL57
PHKG1*Glycogen storage disease due to muscle phosphorylase kinase deficiencyAD/AR
POLGPOLG-related ataxia neuropathy spectrum disorders, Sensory ataxia, dysarthria, and ophthalmoparesis, Alpers syndrome, Progressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndromeAD/AR71265
PYGMGlycogen storage diseaseAR32153
RBCK1Polyglucosan body myopathyAR814
RRM2BProgressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndromeAD/AR4241
RYR1Central core disease, Malignant hyperthermia, Minicore myopathy with external ophthalmoplegia, Centronuclear myopathy, Minicore myopathy, Multicore myopathyAD/AR123563
SLC22A5Carnitine deficiency, systemic primaryAR58118
SUCLA2Mitochondrial DNA depletion syndromeAR826
TK2Mitochondrial DNA depletion syndromeAR3844
TYMPMitochondrial DNA depletion syndromeAR9892
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Blueprint Genetics offers a comprehensive metabolic myopathy and rhabdomyolysis panel that covers classical genes associated with glycogen storage disease, lipid storage disorder, metabolic myopathies and rhabdomyolysis. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ81479
DEL/DUP81479


ICD codes

Commonly used ICD-10 codes when ordering the Metabolic Myopathy and Rhabdomyolysis Panel

ICD-10Disease
G73.6Metabolic myopathies
E74.0Glycogen storage disease
E75Lipid storage disorder
M62.82Rhabdomyolysis

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.