Indian Journal of Clinical Biochemistry

, Volume 26, Issue 4, pp 347–353 | Cite as

Diagnosis of Major Organic Acidurias in Children: Two Years Experience at a Tertiary Care Centre

  • M. P. Narayanan
  • Vaidyanathan Kannan
  • K. P. Vinayan
  • D. M. Vasudevan
Original Article


Organic acid disorders are inherited metabolic disorders in which organic acids accumulate in tissues and biological fluids of affected individuals. Classical organic acidurias include methylmalonic aciduria, propionic aciduria, isovaleric aciduria and maple syrup urine disease (MSUD). They are considered the most frequent metabolic disorders among severely ill children. Patients frequently present with acute symptoms early in life. 420 cases clinically suspected to have organic aciduria, with upper age limit of 12 years for a 2-year period (January 2007–December 2008) were enrolled into this study. Metabolic acidosis and neurological symptoms were the most common signs. Screening tests and thin layer chromatography were done for detection of organic acidurias. Identification and quantitation of organic acids in urine and quantification of amino acids in blood were done by high performance liquid chromatography. Out of 420 patients, 45 patients (10.7%) were found to have organic acidurias. 15 cases of methylmalonic aciduria, 16 cases of propionic aciduria, 13 cases of MSUD, and one case of isovaleric aciduria were diagnosed. Results demonstrate the importance of testing for organic acidurias. Since organic aciduria may cause irreversible brain damage if not treated, we recommend selective screening amongst severely ill children despite implied extra costs.


Inborn errors of metabolism Metabolic screening Organic acidemias Organic acids Organic acid disorders 



NMP is Senior Research Fellow of Indian Council of Medical Research (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.


  1. 1.
    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.PubMedCrossRefGoogle Scholar
  2. 2.
    Rama Devi AR, Naushad SM. Newborn screening in India. Indian J Pediatr. 2004;71(2):157–60.PubMedCrossRefGoogle Scholar
  3. 3.
    Carmencita DP, Bradford L. Therrell newborn screening in the Asia Pacific region. J Inherit Metab Dis. 2007;30:490–506.CrossRefGoogle Scholar
  4. 4.
    Wilson JMG, Jungner F. Principles and practice of screening for disease. Public health papers, No. 34. Geneva, Switzerland: World Health Organization; 1968.Google Scholar
  5. 5.
    Ozand PT, Gascon GG. Organic acidurias: a review. Part I. J Chil Neurol. 1991;6:196–219.CrossRefGoogle Scholar
  6. 6.
    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
  7. 7.
    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
  8. 8.
    Wajner M, Barschak AG, Luft AP, Pires R, Grillo E, Lohr A, et al. Organic aciduria: diagnosis in high risk Brazilian patients. J Pediatr Rio J. 2001;77(5):401–6.PubMedGoogle Scholar
  9. 9.
    Hoffmann GF. Selective screening for inborn errors of metabolism-past present and future. Eur J Pediatr. 1994;153(Suppl 1):S2–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Dionisi-Vici C, Deodato F, R¨oschinger W, Rhead W, Wilcken B. ‘Classical’ organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: Long-term outcome and effects of expanded newborn screening using tandem mass spectrometry. J Inherit Metab Dis. 2006;29:383–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Nagaraja D, Mamtha 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. 2010;43(6):581–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Giugliani R, Dutra JC, Barth ML, Dutra-Filho CS, Goldenfum SL, Wajner M. Seven years experience of a reference laboratory for detection of inborn errors of metabolism in Brazil. J Inher Metab Dis. 1991;14:400–2.PubMedCrossRefGoogle Scholar
  13. 13.
    Lee Ki-Young, Jae-Seony So, Hen Tae-Ryeon. Thin layer chromatographic determination of organic acids for rapid identification of bifidobacteria at genus level. J Microbiol Method. 2001;45:1–6.CrossRefGoogle Scholar
  14. 14.
    Joseph MH, Marsden CA. Amino acids and small peptides. In: Lim CK, editor. HPLC of small peptides. Oxford, UK: IRL Press; 1986. p. 13.Google Scholar
  15. 15.
    Allen KR, Khan R, Watson D. Use of diode array detector in investigation of neonatal organic aciduria. Clin Chem. 1985;31(4):561–3.PubMedGoogle Scholar
  16. 16.
    Hariharan M, Naga S, Van Noord T. Systematic approach to the development of plasma amino acid analysis by high-performance liquid chromatography with ultraviolet detection with precolumn derivatization using phenyl isothiocyanate. J Chromatograph Biomed Appl. 1993;621:15–22.CrossRefGoogle Scholar
  17. 17.
    Verma IC. Burden of genetic disorders in India. Indian J Pediatr. 2000;67(12):893–8.PubMedCrossRefGoogle Scholar
  18. 18.
    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
  19. 19.
    Kumta NB. Inborn errors of metabolism (IEM)—an Indian perspective. Indian J of Pediatr. 2005;72:325–32.CrossRefGoogle Scholar
  20. 20.
    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
  21. 21.
    Redddi OS, Kumar CK, Reddy PP. Screening of aminoacidopathies in India. In: Verma IC, editor. Medical genetics in India, vol. 1. Pondichery: Auroma Enterprises; 1978. p. 93–8.Google Scholar
  22. 22.
    Ambani Lm, Patel ZM, Dhareshwar SS. Clinical biochemical and cytogenetic studies in mental retardation. Indian J Med Res. 1984;79:384–7.PubMedGoogle Scholar
  23. 23.
    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.PubMedCrossRefGoogle Scholar
  24. 24.
    Kaur M, Das GP, Verma IC. Inborn errors of amino acid metabolism in North India. J Inher Met Dis. 1994;17:230–3.CrossRefGoogle Scholar
  25. 25.
    Wong V. Neurodegerative diseases in children. Hong Kong Med J. 1997;3:89–95.PubMedGoogle Scholar
  26. 26.
    Lehnert W. Long term results of selective screening for inborn errors of metabolism. Eur J Pediat. 1994;153(Suppl 1):S9–13.CrossRefGoogle Scholar
  27. 27.
    Rashed M, Ozand PT, Aqeel A, Gascon GG. Experience of King Faisal specialists hospital and research center with organic acid disorders. Brain Dev. 1994;16(Suppl):1–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Saudubray JM, Ogier H, Bonnefont JP, Munnich A, Lombes A, Herve F, et al. Clinical approach to inherited metabolic diseases in neonatal period: 20 years survey. J Inher Metab Dis. 1989;12:S25–41.CrossRefGoogle Scholar
  29. 29.
    Borden M. Screening for metabolic disorders. In: Nyhan WI, editor. Amino acid metabolism in clinical medicine. Norwalk, CT, USA: Appleton-Century-Crofts; 1984. p. 401.Google Scholar
  30. 30.
    Mamta N. Muranjan, Pratima Kondurkar. Clinical features of organic acidemias: experience at a tertiary care center in Mumbai. Indian Pediatr. 2001;38:518–24.Google Scholar
  31. 31.
    Tan IK, Gajra B, Lim MSF. Study of inherited metabolic disorders in Singapore-13 years experience. Ann Acad Med Singapore. 2006;35:804–13.PubMedGoogle Scholar
  32. 32.
    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.PubMedCrossRefGoogle Scholar
  33. 33.
    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.Google Scholar

Copyright information

© Association of Clinical Biochemists of India 2011

Authors and Affiliations

  • M. P. Narayanan
    • 1
  • Vaidyanathan Kannan
    • 1
  • K. P. Vinayan
    • 2
  • D. M. Vasudevan
    • 1
  1. 1.Metabolic Disorders Laboratory, Department of BiochemistryAmrita School of Medicine and Research centreKochiIndia
  2. 2.Division of Pediatric NeurologyAmrita Institute of Medical Sciences and Research CentreCochinIndia

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