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Laboratory Evaluations in Inherited Metabolic Diseases

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Nutrition Management of Inherited Metabolic Diseases

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Abstract

Routine laboratory tests are commonly available and include electrolytes, ammonia, lactate, ketones, and carnitine; these are helpful in evaluating whether a patient may have a metabolic disorder.

Metabolic laboratory tests are specialized tests that are reviewed by a biochemical geneticist and include amino acids, acylcarnitines, and organic acids that are helpful for pinpointing a metabolic diagnosis and/or monitoring treatment.

Evaluation of laboratory findings should always include consideration of the patient’s clinical status, such as presence of illness and length of fasting.

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References

  1. Dionisi-Vici C, Rizzo C, Burlina AB, Caruso U, Sabetta G, Uziel G, et al. Inborn errors of metabolism in the Italian pediatric population: a national retrospective survey. J Pediatr. 2002;140(3):321–7.

    Article  PubMed  Google Scholar 

  2. Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. 2000;105(1):e10.

    Article  CAS  PubMed  Google Scholar 

  3. Saudubray JM, Sedel F, Walter JH. Clinical approach to treatable inborn metabolic diseases: an introduction. J Inherit Metab Dis. 2006;29(2–3):261–74.

    Article  PubMed  Google Scholar 

  4. Carmody JB, Norwood VF. A clinical approach to paediatric acid-base disorders. Postgrad Med J. 2012;88(1037):143–51.

    Article  CAS  PubMed  Google Scholar 

  5. Kraut JA, Madias NE. Approach to patients with acid-base disorders. Respir Care. 2001;46(4):392–403.

    CAS  PubMed  Google Scholar 

  6. Kraut JA, Madias NE. Differential diagnosis of nongap metabolic acidosis: value of a systematic approach. Clin J Am Soc Nephrol. 2012;7(4):671–9.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Enns GM. Neurologic damage and neurocognitive dysfunction in urea cycle disorders. Semin Pediatr Neurol. 2008;15(3):132–9.

    Article  PubMed  Google Scholar 

  8. Braissant O, McLin VA, Cudalbu C. Ammonia toxicity to the brain. J Inherit Metab Dis. 2013;36(4):595–612.

    Article  CAS  PubMed  Google Scholar 

  9. Gropman AL, Prust M, Breeden A, Fricke S, VanMeter J. Urea cycle defects and hyperammonemia: effects on functional imaging. Metab Brain Dis. 2013;28(2):269–75.

    Article  CAS  PubMed  Google Scholar 

  10. Gauthier N, Wu JW, Wang SP, Allard P, Mamer OA, Sweetman L, et al. A liver-specific defect of Acyl-CoA degradation produces hyperammonemia, hypoglycemia and a distinct hepatic Acyl-CoA pattern. PLoS One. 2013;8(7):e60581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Coude FX, Sweetman L, Nyhan WL. Inhibition by propionyl-coenzyme A of N-acetylglutamate synthetase in rat liver mitochondria. A possible explanation for hyperammonemia in propionic and methylmalonic acidemia. J Clin Invest. 1979;64(6):1544–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Al-Hassnan ZN, Boyadjiev SA, Praphanphoj V, Hamosh A, Braverman NE, Thomas GH, et al. The relationship of plasma glutamine to ammonium and of glycine to acid-base balance in propionic acidaemia. J Inherit Metab Dis. 2003;26(1):89–91.

    Article  CAS  PubMed  Google Scholar 

  13. Baruteau J, Sachs P, Broue P, Brivet M, Abdoul H, Vianey-Saban C, et al. Clinical and biological features at diagnosis in mitochondrial fatty acid beta-oxidation defects: a French pediatric study of 187 patients. J Inherit Metab Dis. 2013;36(5):795–803.

    Article  CAS  PubMed  Google Scholar 

  14. Beard L, Wymore E, Fenton L, Coughlin CR, Weisfeld-Adams JD. Lethal neonatal hyperammonemia in severe ornithine transcarbamylase (OTC) deficiency compounded by large hepatic portosystemic shunt. J Inherit Metab Dis. 2017;40(1):159–60.

    Article  PubMed  Google Scholar 

  15. Sokollik C, Bandsma RH, Gana JC, van den Heuvel M, Ling SC. Congenital portosystemic shunt: characterization of a multisystem disease. J Pediatr Gastroenterol Nutr. 2013;56(6):675–81.

    Article  PubMed  Google Scholar 

  16. Batshaw ML, Wachtel RC, Cohen L, Starrett A, Boyd E, Perret YM, et al. Neurologic outcome in premature infants with transient asymptomatic hyperammonemia. J Pediatr. 1986;108(2):271–5.

    Article  CAS  PubMed  Google Scholar 

  17. Holecek M. Ammonia and amino acid profiles in liver cirrhosis: effects of variables leading to hepatic encephalopathy. Nutrition. 2015;31(1):14–20.

    Article  CAS  PubMed  Google Scholar 

  18. Jayakumar AR, Norenberg MD. Hyperammonemia in hepatic encephalopathy. J Clin Exp Hepatol. 2018;8(3):272–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Saudubray JM, de Lonlay P, Touati G, Martin D, Nassogne MC, Castelnau P, et al. Genetic hypoglycaemia in infancy and childhood: pathophysiology and diagnosis. J Inherit Metab Dis. 2000;23(3):197–214.

    Article  CAS  PubMed  Google Scholar 

  20. Ficicioglu C, Coughlin CR 2nd, Bennett MJ, Yudkoff M. Very long-chain acyl-CoA dehydrogenase deficiency in a patient with normal newborn screening by tandem mass spectrometry. J Pediatr. 2010;156(3):492–4.

    Article  CAS  PubMed  Google Scholar 

  21. Sass JO. Inborn errors of ketogenesis and ketone body utilization. J Inherit Metab Dis. 2012;35(1):23–8.

    Article  CAS  PubMed  Google Scholar 

  22. Lamers KJ, Doesburg WH, Gabreels FJ, Lemmens WA, Romsom AC, Wevers RA, et al. The concentration of blood components related to fuel metabolism during prolonged fasting in children. Clin Chim Acta. 1985;152(1–2):155–63.

    Article  CAS  PubMed  Google Scholar 

  23. Bonnefont JP, Specola NB, Vassault A, Lombes A, Ogier H, de Klerk JB, et al. The fasting test in paediatrics: application to the diagnosis of pathological hypo- and hyperketotic states. Eur J Pediatr. 1990;150(2):80–5.

    Article  CAS  PubMed  Google Scholar 

  24. Adeva-Andany M, Lopez-Ojen M, Funcasta-Calderon R, Ameneiros-Rodriguez E, Donapetry-Garcia C, Vila-Altesor M, et al. Comprehensive review on lactate metabolism in human health. Mitochondrion. 2014;17:76–100.

    Article  CAS  PubMed  Google Scholar 

  25. Adeva M, Gonzalez-Lucan M, Seco M, Donapetry C. Enzymes involved in l-lactate metabolism in humans. Mitochondrion. 2013;13(6):615–29.

    Article  CAS  PubMed  Google Scholar 

  26. van den Berghe G. Disorders of gluconeogenesis. J Inherit Metab Dis. 1996;19(4):470–7.

    Article  PubMed  Google Scholar 

  27. Robinson BH. Lactic acidemia and mitochondrial disease. Mol Genet Metab. 2006;89(1–2):3–13.

    Article  CAS  PubMed  Google Scholar 

  28. Centerwall WR, Centerwall SA. Phenylketonuria (FOLLING’s disease). The story of its discovery. J Hist Med Allied Sci. 1961;16:292–6.

    Article  CAS  PubMed  Google Scholar 

  29. Guthrie R. Blood screening for phenylketonuria. JAMA. 1961;178(8):863.

    Google Scholar 

  30. Guthrie R, Susi A. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics. 1963;32:338–43.

    Article  CAS  PubMed  Google Scholar 

  31. Moore S, Stein WH. Chromatographic determination of amino acids on sulfonated polystyrene resins. J Biol Chem. 1951;192:663–81.

    Article  CAS  PubMed  Google Scholar 

  32. Woontner M, Goodman S. Chromatographic analysis of amino and organic acids in physiological fluids to detect inborn errors of metabolism. Curr Protoc Hum Genet. 2006. https://doi.org/10.1002/0471142905.hg1702s51

  33. Nasset ES, Heald FP, Calloway DH, Margen S, Schneeman P. Amino acids in human blood plasma after single meals of meat, oil, sucrose and whiskey. J Nutr. 1979;109(4):621–30.

    Article  CAS  PubMed  Google Scholar 

  34. Goodman SI. An introduction to gas chromatography-mass spectrometry and the inherited organic acidemias. Am J Hum Genet. 1980;32(6):781–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Longo N, di San A, Filippo C, Pasquali M. Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet. 2006;142C(2):77–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Stanley CA. Carnitine deficiency disorders in children. Ann N Y Acad Sci. 2004;1033:42–51.

    Article  CAS  PubMed  Google Scholar 

  37. Santra S, Hendriksz C. How to use acylcarnitine profiles to help diagnose inborn errors of metabolism. Arch Dis Child Educ Pract Ed. 2010;95(5):151–6.

    Article  CAS  PubMed  Google Scholar 

  38. 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(3):321–4.

    Article  CAS  PubMed  Google Scholar 

  39. Van Hove JL, Zhang W, Kahler SG, Roe CR, Chen YT, Terada N, et al. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: diagnosis by acylcarnitine analysis in blood. Am J Hum Genet. 1993;52(5):958–66.

    PubMed  PubMed Central  Google Scholar 

  40. Rinaldo P, Cowan TM, Matern D. Acylcarnitine profile analysis. Genet Med. 2008;10(2):151–6.

    Article  PubMed  Google Scholar 

  41. Coene KLM, Kluijtmans LAJ, van der Heeft E, Engelke UFH, de Boer S, Hoegen B, et al. Next-generation metabolic screening: targeted and untargeted metabolomics for the diagnosis of inborn errors of metabolism in individual patients. J Inherit Metab Dis. 2018;41(3):337–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ismail IT, Showalter MR, Fiehn O. Inborn errors of metabolism in the era of untargeted metabolomics and lipidomics. Meta. 2019;9(10):242.

    CAS  Google Scholar 

  43. Almontashiri NAM, Zha L, Young K, Law T, Kellogg MD, Bodamer OA, et al. Clinical validation of targeted and untargeted metabolomics testing for genetic disorders: a 3 year comparative study. Sci Rep. 2020;10(1):9382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Pierpont ME, Judd D, Goldenberg IF, Ring WS, Olivari MT, Pierpont GL. Myocardial carnitine in end-stage congestive heart failure. Am J Cardiol. 1989;64(1):56–60.

    Article  CAS  PubMed  Google Scholar 

  45. Tuchman M, Jaleel N, Morizono H, Sheehy L, Lynch MG. Mutations and polymorphisms in the human ornithine transcarbamylase gene. Hum Mutat. 2002;19(2):93–107.

    Article  CAS  PubMed  Google Scholar 

  46. Caldovic L, Abdikarim I, Narain S, Tuchman M, Morizono H. Genotype-phenotype correlations in ornithine transcarbamylase deficiency: a mutation update. J Genet Genomics. 2015;42(5):181–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hesse J, Braun C, Behringer S, Matysiak U, Spiekerkoetter U, Tucci S. The diagnostic challenge in very-long chain acyl-CoA dehydrogenase deficiency (VLCADD). J Inherit Metab Dis. 2018;41(6):1169–78.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Clinical Genetics and Metabolism, Children’s Hospital Colorado, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA

    Curtis R. Coughlin II

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  1. Curtis R. Coughlin II
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Correspondence to Curtis R. Coughlin II .

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Editors and Affiliations

  1. Children’s Hospital Colorado, University of Colorado Hospital, Aurora, CO, USA

    Laurie E. Bernstein

  2. Met Ed Co, Boulder, CO, USA

    Fran Rohr

  3. Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA

    Sandy van Calcar

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Coughlin, C.R. (2022). Laboratory Evaluations in Inherited Metabolic Diseases. In: Bernstein, L.E., Rohr, F., van Calcar, S. (eds) Nutrition Management of Inherited Metabolic Diseases. Springer, Cham. https://doi.org/10.1007/978-3-030-94510-7_7

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  • DOI: https://doi.org/10.1007/978-3-030-94510-7_7

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