Genes Included

ACAD9, ACADM, ACADS, ACADVL, ACAT1, AGL, ALDOA, ALDOB, CPT1A, CPT2, DECR1, ENO3, ETFA, ETFB, ETFDH, FBP1, G6PC, GAA, GBE1, GLUD1, GYS1, GYS2, HADH, HADHA, HADHB, HMGCL, HSD17B10, LAMP2, LPIN1, MLYCD, MPI, NADK2, OXCT1, PC, PCK1,  PCK2, PFKM, PGAM2, PGK1, PGM1, PHKA1, PHKA2, PHKB, PHKG2, PPARG, PRKAG2, PYGL, PYGM, SLC22A5, SLC25A20, SLC2A2, SLC37A4, SLC52A2, SLC52A3, TANGO2, TAZ

Description

The Metaboseq panel is designed for patients with unexplained hypoglycemia, rhabdomyolysis, and other features of an inborn error of metabolism such as metabolic hypoglycemia, liver dysfunction, rhabdomyolysis, or cardiomyopathy syndromes. The panel includes genes associated with glycogen storage disorders, fatty acid oxidation disorders, and a number of other conditions that can present in a similar manner. 

Indications

Unexplained hypoglycemia
Rhabdomyolysis and skeletal myopathy
Metabolic acidosis
Hepatomegaly, liver dysfunction and cirrhosis 
Hypotonia, muscle cramps/ pain
Cardiomyopathy/ arrhythmias
Respiratory distress
Hepatic encephalopathy 
Growth retardation
Fatigue

Testing Methodology 

This test is performed by enrichment of the coding exons, flanking intronic and untranslated regions (5’ and 3’), as well as known pathogenic variants (HGMD 2017.3) in the promoter and deep intronic regions of the genes specified above using oligonucleotide probe hybridization followed by next-generation sequencing with >50X coverage at every target base. All pathogenic and novel variants, as well as variants of unknown (indeterminate) significance, as determined bioinformatically, are confirmed by Sanger sequencing. Regions with <50X will be filled in by Sanger sequencing. A detailed non-coding variant list is available upon request.

Sensitivity and Limitations

The analytical sensitivity of DNA sequencing is over 99% for the detection of nucleotide base changes, small deletions and insertions in the regions analyzed. Variants in regulatory regions and non-reported variants in untranslated regions may not be detected by this test. Large deletions/ duplications, large insertions and other complex genetic events will not be identified using sequencing methodology. 

Turn-Around Time

28 days

CPT Codes

81443

How to Order

Download Inborn Errors of Metabolism requisition

References

Bhattacharya, K. (2015) Investigation and management of the hepatic glycogen storage diseases. Transl Pediatr. 4(3):240-8.

Burda, P and Hochuli, M. (2015) Hepatic glycogen storage disorders: what have we learned in recent years? Curr Opin Clin Nutr Metab Care. 18(4):415-21.

Chandramouli, C, Varma, U, et al. (2015) Myocardial glycogen dynamics: new perspectives on disease mechanisms. Clin Exp Pharmacol Physiol. 42(4):415-25.

El-Gharbawy, A and Vockley J. (2018) Inborn Errors of Metabolism with Myopathy: Defects of Fatty Acid Oxidation and the Carnitine Shuttle System. Pediatr Clin North Am. 65(2):317-335.

Foley, AR, Menezes, MP, et al. (2014) Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain 137: 44-56. 

Frerman, FE and Goodman, SI. (2001) Defects of electron transfer flavoprotein and electron transfer flavoprotein-ubiquinone oxidoreductase: glutaric acidemia type II. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Metabolic and Molecular Bases of Inherited Disease. (8th ed.) New York: McGraw-Hill (pub.). Pp. 2357-2365.

Green, P, Wiseman, M, et al. (2010) Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in C20ORF54. Am. J. Hum. Genet. 86: 485-489.

Jackson, S, Kler, RS, et al. (1992) Combined enzyme defect of mitochondrial fatty acid oxidation. J. Clin. Invest. 90: 1219-1225.

Kanungo, S, Wells K, et al. (2018) Glycogen metabolism and glycogen storage disorders. Ann Transl Med. 6(24):474.

Kilimann, MW and Oldfors, A. (2015) Glycogen pathways in disease: new developments in a classical field of medical genetics. J Inherit Metab Dis. 38(3):483-7.

Longo, N, di San Filippo, CA, et al. (2006) Disorders of carnitine transport and the carnitine cycle. Am. J. Med. Genet. 142C: 77-85.

Merritt, JL 2nd, Norris, M, et al. (2018) Fatty acid oxidation disorders. Ann Transl Med. 6(24):473.

Stone, WL and Adil, A. Glycogen Storage Disease. StatPearls [Internet].

Sun, B, Brooks, ED, et al. (2015) Preclinical Development of New Therapy for Glycogen Storage Diseases. Curr Gene Ther. 15(4):338-47.

Weinstein, DA, Steuerwald, U et al. (2018) Inborn Errors of Metabolism with Hypoglycemia: Glycogen Storage Diseases and Inherited Disorders of Gluconeogenesis. Pediatr Clin North Am. 65(2):247-265.