Skip to main content
SpringerLink
Log in

Organic Acidurias: An Updated Review

  • Review Article
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Organic acidurias are an important class of inherited metabolic disorders arising due to defect in intermediary metabolic pathways of carbohydrate, amino acids and fatty acid oxidation. This review summarizes the current knowledge about the important organic acidurias in the Indian population. Specifically, diagnosis and principles of treatment of organic acidurias are covered. The salient features of common organic acidurias as well as their prevalence in various parts of the world are reviewed in some detail.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ozand PT, Gascon GG. Organic acidurias: a review. Part I. J Chil Neurol. 1991;6:196–219.

    Article  CAS  Google Scholar 

  2. Chalmers RA, Lawson AM. Organic acids in man. Analytical chemistry, biochemistry and diagnosis of the organic acidurias. 1st ed. London: Chapman and Hall; 1982.

    Google Scholar 

  3. Wajner M, Wannmacher CMD, Gaidzinski D, Dutra Filho CS. Detection of inborn errors of metabolism in patients of pediatric intensive care units of Porto Alegre, Brazil. Comparison between the prevalence of such disturbances in a selected and an unselected sample. Braz J Genet. 1986;9:331–40.

    Google Scholar 

  4. Wajner M, Barschak AG, Luft AP, Pires R, Grillo E, Lohr A, et al. Organic aciduria: diagnosis in high risk Brazilian patients. J Pediatr 2001;77(5), 401–6.

    Google Scholar 

  5. Hoffmann GF. Selective screening for inborn errors of metabolism-past present and future. Eur J Pediatr. 1994;153(Suppl 1):S2–8.

    Article  PubMed  CAS  Google Scholar 

  6. Wanmacheer CMD, Wajner M, Giugliani R, Giugliani ERJ, Costa MG, Giugliani MCK. Detection of metabolic disorders among high-risk patients. Rev Brasil Genet. 1982;5:187–94.

    Google Scholar 

  7. Coelho JC, Wajner M, Burin MG, Vargas CR, Giugliani R. Selective screening of 10,000 high- risk Brazilian patients for the detection of inborn errors of metabolism. Eur J Pediatr. 1997;156:650–4.

    Article  PubMed  CAS  Google Scholar 

  8. Green A. Guide to diagnosis of inborn errors of metabolism in district general hospital. J Clin Pathol. 1989;42:84–91.

    Article  PubMed  CAS  Google Scholar 

  9. Blau N, van Spronsen FJ, Levy HL. Phenylketonuria. Lancet. 2010;376(9750):1417–27.

    Google Scholar 

  10. van Spronsen FJ. Phenylketonuria: a 21st century perspective. Nat Rev Endocrinol. 2010;6(9):509–14.

    Article  PubMed  Google Scholar 

  11. Zhan JY, Qin YF, Zhao ZY. Neonatal screening for congenital hypothyroidism and phenylketonuria in China. World J Pediatr. 2009;5(2):136–9.

    Article  PubMed  Google Scholar 

  12. Niu DM, Chien YH, Chiang CC, Ho HC, Hwu WL, Kao SM, Chiang SH, Kao CH, Liu TT, Chiang H, Hsiao KJ. Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan. J Inherit Metab Dis. 2010;33(Suppl 2):S295–305.

    Article  PubMed  Google Scholar 

  13. Seymour CA, Thomason MJ, Chalmers RA, Addison GM, Bain MD, Cockburn F,Littlejohns P, Lord J, Wilcox AH. Newborn screening for inborn errors of metabolism: a systematic review. Health Technol Assess. 1997;1(11):i–iv, 1–95.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  15. Loeber JG. Neonatal screening in Europe; the situation in 2004. J Inherit Metab Dis. 2007;30(4):430–8.

    Article  PubMed  Google Scholar 

  16. Narayanan MP, Vaidyanathan K, Vinayan KP, Vasudevan DM. Diagnosis of major organic acidurias: two years experience at a tertiary care center. Indian J Clin Biochem (Accepted for publication).

  17. Frazier DM, Millington DS, McCandless SE, Koeberl DD, Weavil SD, Chaing SH, Muenzer J. The tandem mass spectrometry newborn screening experience in North Carolina: 1997–2005. J Inherit Metab Dis. 2006;29(1):76–85.

    Article  PubMed  CAS  Google Scholar 

  18. Verma IC. Burden of genetic disorders in India. Indian J Pediatr. 2000;67(12):893–8.

    Article  PubMed  CAS  Google Scholar 

  19. ICMR collaborating centers & central coordinating unit. Multicentric study on genetic causes of mental retardation in India. Indian J Med Res. 1991;94:161–9.

    Google Scholar 

  20. Choudhuri T, Sengupta S. Inborn errors of metabolism—an Indian perspective. Int J Hum Genet. 2006;6(1):89–91.

    Google Scholar 

  21. Hoffmann GF, Gibson KM, Trefz FK, Nyhan WL, Bremer HJ, Rating D. Neurological manifestations of organic acid disorders. Eur J Pediatr. 1994;153(Supplement 1):S94–100.

    Article  PubMed  CAS  Google Scholar 

  22. Kumps A, Duez P, Mardens Y. Metabolic, nutritional, iatrogenic, and artifactual sources of urinary organic acids: a comprehensive table. Clin Chem 2002;48(5):708–17.

    Google Scholar 

  23. Yannicelli S. Nutrition therapy of organic acidaemias with amino acid-based formulas: emphasis on methylmalonic and propionic acidaemia. J Inherit Metab Dis 2006;29:281–7.

    Google Scholar 

  24. Thompson GN, Chalmers RA. Increased urinary metabolite excretion during fasting in disorders of propionate metabolism. Part 1 of 4. Pediatr Res. 1990;27:413–6.

    Article  PubMed  CAS  Google Scholar 

  25. Chalmers RA, Stacey TE, Tracey BM, et al. L-Carnitine: insufficiency in disorders of organic acid metabolism: response to L-carnitine by patients with methylmalonic aciduria and 3-hydroxy-3-methylglutaric aciduria. J Inherit Metab Dis. 1984;7:109–10.

    Article  PubMed  Google Scholar 

  26. Burlina AB, Bonafe L, Zacheloo F. Clinical and biochemical approach to the neonate with a suspected inborn error of amino acid and organic acid metabolism. Sem Perinatol. 1999;23:162–73.

    Article  CAS  Google Scholar 

  27. Ambani LM, Patel ZM, Dhareshwar SS. Clinical biochemical and cytogenetic studies in mental retardation. Indian J Med Res. 1984;79:384–7.

    PubMed  CAS  Google Scholar 

  28. Kumta NB. Inborn errors of metabolism (IEM)—an Indian perspective. Indian J Pediatr. 2005;72:325–32.

    Article  PubMed  CAS  Google Scholar 

  29. Rama Rao BSS, Subhash MN, Narayanan HS. Metabolic anomalies detected during a systematic biochemical screening of mentally retarded cases. Indian J Med Res. 1977;65:241–5.

    Google Scholar 

  30. Reddi OS, Kumar CK, Reddy PP. Screening of aminoacidopathies in India. In Verma IC editors. Medical genetics in India, Vol. 1 Pondichery: Auroma Enterprises 1978;93–8.

  31. Devi ARR, Rao NA, Bittles AH. Inbreeding and the incidence of childhood genetic disorders in Karnataka, South India. J Med Genet. 1987;24:362–5.

    Article  PubMed  CAS  Google Scholar 

  32. Kaur M, Das GP, Verma IC. Inborn errors of amino acid metabolism in North India. J Inherit Met Dis. 1994;17:230–3.

    Article  CAS  Google Scholar 

  33. Swarna M, Jyothy A, Usha Rani P, Reddy PP. Amino acid disorders in mental retardation: a two-decade study from Andhra Pradesh. Biochem Genet. 2004;42(3–4):85–98.

    Article  PubMed  CAS  Google Scholar 

  34. Uma SM, Jyothy A, Reddy PP, Reddi O. Aminoacidopathies in Andhra Pradesh; report of a screening programme. J Inherit Metab Dis. 1982;5(4):211–4.

    Article  PubMed  CAS  Google Scholar 

  35. Rao AN, Kavitha J, Koch M, Suresh Kumar V. Inborn errors of metabolism: review and data from a tertiary care center. Indian Journal of Clinical Biochemistry. 2009;24(3):215–22.

    Article  CAS  Google Scholar 

  36. Agarwal RL, Muranjan MN. Diagnostic practice for organic acidemias: barriers to early diagnosis. Arch Dis Child 2008;93;1000.

  37. Nagaraja D, Mamatha SN, De T, Christopher R. Screening for inborn errors of metabolism using automated electrospray tandem mass spectrometry: study in high-risk Indian population. Clin Biochem 2009.

  38. Muranjan MN, Kondurkar P. Clinical features of organic acidemias: experience at a tertiary care center in Mumbai. Indian Pediatr. 2001;38:518–24.

    PubMed  CAS  Google Scholar 

  39. Chalmers RA, Watts RWE, Lawson AM. A comprehensive screening method for detecting organic acidurias and other metabolic diseases in acutely sick infants and children. Ann Clin Biochem. 1977;14:149–56.

    PubMed  CAS  Google Scholar 

  40. Sanderson S, Green A, Preece MA, Burton H. The incidence of inherited metabolic disorders in the west midlands UK. Arch Dis Child. 2006;91(11):869–99.

    Article  Google Scholar 

  41. Satwani H, Raza J, Hanai J, Nomachi S. Prevalence of selected disorders of inborn errors of metabolism in suspected cases at a tertiary care hospital in Karachi. J Pak Med Assoc. 2009;59(12):815–9.

    PubMed  Google Scholar 

  42. Filiano JJ, Bellimer SG, Kunz PL. Tandem mass spectrometry and newborn screening: pilot data and review. Pediatr Neurol. 2002;26:201–4.

    Article  PubMed  Google Scholar 

  43. Glass HC, Feigenbaum A, Clarke JTR. A study on the nature of genetic metabolic practice at a major pediatric referral centre. J Inherit Metab Dis. 2006;29:175–8.

    Article  PubMed  CAS  Google Scholar 

  44. Dionisi-Vici C, Deodato F, Röschinger W, et al. ‘Classical’ organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: Longterm outcome and effects of expanded newborn screening using tandem mass spectrometry. J Inherit Metab Dis. 2006;29:383–9.

    Article  PubMed  CAS  Google Scholar 

  45. Han LS, Ye J, Qiu WJ, Gao XL, Wang Y, Gu XF. Selective screening for inborn errors of metabolism on clinical patients using tandem mass spectrometry in china: a four-year report. J Inherit Metab Dis. 2007;30(4):507–14.

    Article  PubMed  CAS  Google Scholar 

  46. Tan I-K, Gajra B, Lim MSF. Study of inherited metabolic disorders in Singapore-13 Years experience. Ann Acad Med Singapore 2006;35:804–13.

    Google Scholar 

  47. Hori D, Hasegawa Y, Kimura M, Yang Y, Verma IC, Yamaguchi S. Clinical onset and prognosis of Asian children with organic acidemias, as detected by analysis of urinary organic acids using GC/MS, instead of mass screening. Brain Dev. 2005;27:39–45.

    Article  PubMed  Google Scholar 

  48. Song Y-Z, Li B-X, Hao H, Xn R-L, Zhang T, Zhang C-H, et al. Selective screening for inborn errors of metabolism and secondary methylmalonic aciduria in pregnancy at high risk district of neural tube defects: a human metabolome study by GC-MS in China. Clin Chem. 2008;41:616–20.

    CAS  Google Scholar 

  49. Moammar H, Cheriyan G, Mathew R, Al-Sannaa N. Incidence and pattern of inborn errors of metabolism in the Eastern province of Saudi Arabia 1983–2008. Ann Saudi Med. 2010;30(4):271–7.

    Article  PubMed  Google Scholar 

  50. Wajner M, Coelho Dde M, Ingrassia R, de Oliveira AB, Busanello EN, Raymond K et al. Selective screening for organic acidemias by urine organic acid GC-MS analysis in Brazil: fifteen-year experience. Clin Chim Acta. 2009;400(1–2):77–81.

    Google Scholar 

  51. Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular bases of inherited disease, 7th ed. New York: Mc Graw-Hill 2001:1.

Download references

Acknowledgments

NMP is Senior Research Fellow of ICMR, Financial assistance received from Kerala state Council for Science, Technology and Environment (KSCSTE), Government of Kerala, Indian Council of Medical Research (ICMR), Government of India is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Metabolic Disorders Division, Amrita Institute of Medical Science, AIMS Ponekkara PO, Kochi, Kerala, 682 041, India

    Kannan Vaidyanathan, M. P. Narayanan & D. M. Vasudevan

Authors
  1. Kannan Vaidyanathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. P. Narayanan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. M. Vasudevan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kannan Vaidyanathan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vaidyanathan, K., Narayanan, M.P. & Vasudevan, D.M. Organic Acidurias: An Updated Review. Ind J Clin Biochem 26, 319–325 (2011). https://doi.org/10.1007/s12291-011-0134-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12291-011-0134-2

Keywords

Search

Navigation