Across all of our panels, we provide improved clinical usefulness, increased diagnostic yield, empowered differential diagnosis, and analytically validated current genes. High-quality coverage of difficult-to-sequence genes enables natural diagnostic effects in complex patient scenarios.
There are hundreds of inherited metabolic disorders have been discovered, such as lysosomal storage, fatty acid oxidation, creatine metabolism, glycosylation, glycogen storage, urea cycle disorders, peroxisomal disorders, organic acidemias, hypoglycemia, hyperinsulinism, ketone metabolism deficiency, lipodystrophy, hyperphenylalaninemia, and mitochondrial DNA depletion. These illnesses can result in lifelong health issues or even death, and they range in severity and age of onset. It is essential to identify congenital metabolic diseases. Addressing the hereditary condition before time is vital to prevent adverse outcomes such as morbidity, mortality, and impairments.
The most effective method for sub-typing metabolic diseases is genetic diagnostics, which also gives the data required to make knowledgeable, tailored therapy and management decisions. A precise diagnosis is crucial, for instance, in the case of coenzyme q10 insufficiency, since specific individuals may respond well to CoQ10 therapy. As another illustration, nine distinct types of lysosomal storage illnesses can be treated using enzyme replacement therapy (ERT), each of which substitutes or enhances the activity of a specific endogenous catabolic enzyme found in cellular lysosomes.
In 2015, a study conducted by the UK showed that Genetic Testing Network, genetic testing for metabolic myopathy, rhabdomyolysis, and fatty acid metabolism is thought to be cost-effective for public health systems. Additionally, genetic diagnosis is regarded as a valuable tool for assessing the risk of family members. Starting preventative therapies and giving lifestyle advice is feasible if at-risk relatives are identified. It also supports frequent follow-ups by medical experts. Additionally, identifying the causal mutation indicates the family’s pattern of inheritance, which is necessary for informed genetic counseling. Further, genetic testing might be helpful in family planning.
The Metabolic Panel is designed to detect single nucleotide variants (SNVs) and small insertions and deletions in 63genes associated with neurological risk. Targeted regions for this panel include the coding exons and 10 bp intronic sequencesimmediate to the exon-intron boundary of each coding exon in each of these genes. Extracted patient DNA is prepared using targetedhybrid capture, assignment of a unique index, and sequencing via Illumina sequencing by synthesis (SBS) technology. Data is alignedusing human genome build GRCh37. Variant interpretation is performed according to current American College of Medical Geneticsand Genomics (ACMG) professional guidelines for the interpretation of germline sequence variants using Fabric EnterpriseTM Pipeline6.6.15. Variant interpretation and reporting is performed by Fabric Clinical (CLIA ID: 45D2281059 and CAP ID: 9619501). The followingquality filters are applied to all variants: quality <500, allelic balance <0.3, coverage <10x.
ABCD1 AGL ASS1 ATP7B BCKDHA BCKDHB CLCNKB DYSF FAH FXN GALT GLA HEXA LAMA2 LAMP2 MT-ND5 OTC PAH PCCA PCCB RAI1 ABCC8 BLK EIF2AK3 FOXP3 GATA6 GCK GLIS3 GLUD1 HADH HNF1A HNF1B HNF4A INS INSR KCNJ11 KLF11 NEUROD1 NEUROG3 PAX4 PDX1 PPARG PTF1A RFX6 SLC16A1 SLC2A2 WFS1 ZFP57
This test aims to detect all clinically relevant variants within the coding regions of the genes evaluated. Pathogenic and likelypathogenic variants detected in these genes should be confirmed by orthogonal methods. Detected genetic variants classified asbenign, likely benign, or of uncertain significance are not included in this report. Homopolymer regions and regions outside of thecoding regions cannot be captured by the standard NGS target enrichment protocols. At this time, the assay does not detect largedeletions and duplications. This analysis also cannot detect pathogenic variants within regions which were not analyzed (e.g., introns,promoter and enhancer regions, long repeat regions, and mitochondrial sequence). This assay is not designed to detect mosaicismand is not designed to detect complex gene rearrangements or genomic aneuploidy events. It is important to understand that theremay be variants in these genes undetectable using current technology. Additionally, there may be genes associated with neurologicalpathology whose clinical association has not yet been definitively established. The test may therefore not detect all variantsassociated with neurological pathology. The interpretation of variants is based on our current understanding of the genes in this paneland is based on current ACMG professional guidelines for the interpretation of germline sequence variants. Interpretations maychange over time as more information about the genes in this panel becomes available. Qualified health care providers should beaware that future reclassifications of genetic variants can occur as ACMG guidelines are updated. Factors influencing the quantityand quality of extracted DNA include, but are not limited to, collection technique, the amount of buccal epithelial cells obtained, thepatient’s oral hygiene, and the presence of dietary or microbial sources of nucleic acids and nucleases, as well as other interferingsubstances and matrix-dependent influences. PCR inhibitors, extraneous DNA, and nucleic acid degrading enzymes may adverselyaffect assay results.
This laboratory developed test (LDT) was developed and its performance characteristics were determined by PreCheck HealthServices, Inc. This test was performed at PreCheck Health Services, Inc. (CLIA ID: 10D2210020 and CAP ID: 9101993) that is certifiedunder the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as qualified to perform high complexity testing. This assayhas not been cleared or approved by the U.S. Food and Drug Administration (FDA). Clearance or approval by the FDA is not requiredfor the clinical use of this analytically and clinically validated laboratory developed test. This assay has been developed for clinicalpurposes and it should not be regarded as investigational or for research.
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4. Christacos NC, Fridovich-Keil JL. Molecular genetics and metabolism. 2002, Aug. Impact of patient mutations on heterodimer formation and function in human galactose-1-P uridylyltransferase. (PMID: 12208137)
5. Dobrowolski SF, Banas RA, Suzow JG, Berkley M, et al. The Journal of molecular diagnostics : JMD. 2003, Feb. Analysis of common mutations in the galactose-1-phosphate uridyl transferase gene: new assays to increase the sensitivity and specificity of newborn screening for galactosemia. (PMID: 12552079)
6. Bosch AM, Ijlst L, Oostheim W, Mulders J, et al. Human mutation. 2005, May. Identification of novel mutations in classical galactosemia. (PMID: 15841485)
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