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Testing Modalities for Inborn Errors of Metabolism — What a Clinician Needs to Know?

  • Rational Diagnostics
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Abstract

The present century is being hailed as the century for genetic therapies, and inborn errors of metabolism is leading the way. As we gear ourselves for treating children with genetic and metabolic disorders, the key is to recognize them early and accurately for best outcomes. In these changing times with advent of technology, clinicians are now more aware, exposed and well equipped with the armamentarium of diagnostic modalities. However, it is difficult to choose between the tests without a baseline knowledge about testing for genetic and metabolic disorders. The key question for a clinician when dealing with a suspected metabolic disorder case is ‘what test to order’ and ‘how to proceed.’ The current article provides a rational view on the various laboratory testing modalities available for diagnosis of inborn errors of metabolism. The article provides details of the basic and advanced metabolic tests that can be ordered in appropriate settings.

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References

  1. Sample Registration System (SRS) Bulletin. Office of Registrar General of India (for the year 2017). 2019; 52 (1). Available From: censusindia.gov.in/vital_statistics/SRS_Bulletins/SRS_Bulletin-Rate-2017-_May_2019.pdf. Accessed May 24, 2019.

  2. Garrod AE. Inborn errors of metabolism. In: Frowde H, Hodder and Stoughton, editors. The Croanian Lectures Delivered Before the Royal College of Physicians of London in June 1908. London: Oxford University Press; 1909.

    Google Scholar 

  3. Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969–1996. Pediatr. 2000;105:e10.

    Article  CAS  Google Scholar 

  4. Bijarnia-Mahay S, Arora V, Puri RD, Lall M, Saxena R, Verma J, et al. The changing scenario in prenatal diagnosis of genetic disorders: Genetics to genomics. Curr Med Res Prac. 2018; 8:203–8.

    Article  Google Scholar 

  5. Vernon HJ. Inborn errors of metabolism: Advances in diagnosis and therapy. JAMA Pediatr. 2015;169:778–82.

    Article  Google Scholar 

  6. Scriver CR, Beaudet AL, Sly WS, Valle D, Vogelstein B, editors. The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID). New York: McGraw-Hill; 2018.

    Google Scholar 

  7. Blau N, Duran M, Gibson KM, Dionisi-Vici C, editors. Physician’s Guide to the Diagnosis, Treatment, and Follow-up of Inherited Metabolic Diseases. Berlin: Springer Nature; 2014.

    Google Scholar 

  8. Saudubray JM, van den Berghe G, Walter J, editors, 6th ed. In born Metabolic Diseases: Diagnosis and Treatment. Berlin: Springer; 2016.

    Google Scholar 

  9. Nyhan WL. When to suspect metabolic disease. In: Hoffmann GF, Zschocke J, Nyhan WL Eds. Inherited Metabolic Diseases: A Clinical Approach. 2nd ed. Berlin: Springer; 2017. p.19–28.

    Chapter  Google Scholar 

  10. El-Hattab AW. Inborn errors of metabolism. Clin Perinatol. 2015; 42:413–39.

    Article  Google Scholar 

  11. Gibson K, Duran M. Simple metabolic screening tests. In: Blau N, Duran M, Gibson K, editors. Laboratory Guide to the Methods in Biochemical Genetics. Berlin: Springer; 2008. p. 22–33.

    Google Scholar 

  12. Garg U, Smith LD, Heese BA. Introduction to the laboratory diagnosis of inherited metabolic diseases. In: Garg U, Smith LD, Heese BA, editors. Laboratory Diagnosis of Inherited Metabolic Diseases. Washington: AACC press; 2012. p. 1–12.

    Google Scholar 

  13. Clayton PT. Inborn errors presenting with liver dysfunction. Semin Neonatol. 2002; 7:49–63.

    Article  Google Scholar 

  14. Alam S, Lal BB. Metabolic liver diseases presenting as acute liver failure in children. Indian Pediatr. 2016;53:695–701.

    Article  Google Scholar 

  15. Verma J, Thomas DC, Kasper DC, Sharma S, Puri RD, Bijarnia-Mahay S, et al. Inherited metabolic disorders: Efficacy of enzyme assays on dried blood spots for the diagnosis of lysosomal storage disorders. JIMD Rep. 2017;31:15–27.

    Article  Google Scholar 

  16. Bijarnia-Mahay S, Movva S, Gupta N, Sharma D, Puri RD, Kotecha U, et al. Molecular diagnosis of hereditary fructose intolerance: Founder mutation in a community from India. JIMD Rep. 2015;19:85–93.

    Article  Google Scholar 

  17. Millington DS, Kodo N, Norwood DL, Roe CR. Tandem mass spectrometry: A new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism. J Inherit Metab Dis 1990;13:321–4.

    Article  CAS  Google Scholar 

  18. Ho CS, Lam CW, Chan MH, Cheung RC, Law LK, Lit LC, et al. Electrospray ionization mass spectrometry: Principles and clinical applications. Clin Biochem Rev. 2003; 24:3–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Mass Spectrometry- Atomic Particles Stored in a Cage Without Material Walls. Avialable from:URL: https://www.biologie.hu-berlin.de/de/gruppenseiten/oekologie/meth/massspec/mass.sp. Accessed May 24, 2019.

  20. Wilcken B. Recent advances in newborn screening. J Inherit Metab Dis. 2007;30:129–133.

    Article  CAS  Google Scholar 

  21. Lehotay DC, Hall P, Lepage J, Eichhorst JC, Etter ML, Greenberg CR. LC-MS/MS progress in newborn screening. Clin Biochem. 2011;44:21–31.

    Article  CAS  Google Scholar 

  22. Fu X, Iga M, Kimura M, Yamaguchi S. Simplified screening for organic acidemia using GC/MS and dried urine filter paper: a study on neonatal mass screening. Early Hum Dev. 2000;58:41–55.

    Article  CAS  Google Scholar 

  23. Narayan SB, Ditewig-Meyers G, Graham KS, Scott R, Bennett MJ. Measurement of plasma amino acids by Ultraperformance® Liquid Chromatography. Clin Chem Lab Med. 2011; 49:1177–85.

    Article  CAS  Google Scholar 

  24. Jaeken J, van Eijk HG, van der Heul C, Corbeel L, Eeckels R, Eggermont E. Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome. Clin Chim Acta 1984; 144:245–7.

    Article  CAS  Google Scholar 

  25. Prasad R, Stout RL, Coffin D, Smith J. Analyses of carbohydrate deficient transferrin by capillary zone electrophoresis. Electrophoresis. 1997;18:1814–8.

    Article  CAS  Google Scholar 

  26. Jaeken J. Congenital disorders of glycosylation. Ann N Y Acad Sci. 2010;1214:190–8.

    Article  CAS  Google Scholar 

  27. Li X, Raihan MA, Reynoso FJ, He M. Glycosylation analysis for congenital disorders of glycosylation. Curr Protoc Hum Genet. 2015;86:1–22.

    CAS  Google Scholar 

  28. Tebani A, Abily-Donval L, Afonso C, Marret S, Bekri S. Clinical metabolomics: The new metabolic window for inborn errors of metabolism investigations in the post-genomic era. Int J Mol Sci. 2016;17.pii:E1167.

    Article  Google Scholar 

  29. Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA. 1997;74:5463–7.

    Article  Google Scholar 

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Authors and Affiliations

  1. Sir Ganga Ram Hospital, Institute of Medical Genetics and Genomics, Rajinder Nagar, New Delhi, 110 060, India

    Sunita Bijarnia-Mahay

  2. Division of Genetics, Department of Pediatrics, Maulana Azad Medical College and associated Lok Nayak Hospital, New Delhi, India

    Seema Kapoor

Authors
  1. Sunita Bijarnia-Mahay
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  2. Seema Kapoor
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Correspondence to Sunita Bijarnia-Mahay.

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Bijarnia-Mahay, S., Kapoor, S. Testing Modalities for Inborn Errors of Metabolism — What a Clinician Needs to Know?. Indian Pediatr 56, 757–766 (2019). https://doi.org/10.1007/s13312-019-1637-9

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  • DOI: https://doi.org/10.1007/s13312-019-1637-9

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