Abstract
Introduction: Maple Syrup Urine Disease (MSUD) is an autosomal recessive disorder caused by defects in the branched-chain α-ketoacid dehydrogenase complex resulting in accumulation of branched-chain amino acids (BCAAs) and corresponding branched-chain ketoacids (BCKAs) in tissues and plasma, which are neurotoxic. Early diagnosis and subsequent nutritional modification management can reduce the morbidity and mortality. Prior to 1990s, the diagnosis of MSUD and other inborn errors of metabolism (IEM) in Malaysia were merely based on clinical suspicion and qualitative one-dimensional thin layer chromatography technique. We have successfully established specific laboratory diagnostic techniques to diagnose MSUD and other IEM. We described here our experience in performing high-risk screening for IEM in Malaysia from 1999 to 2006. We analysed the clinical and biochemical profiles of 25 patients with MSUD.
Methods: A total of 12,728 plasma and urine samples from patients suspected of having IEM were received from physicians all over Malaysia. Plasma amino acids quantitation using fully automated amino acid analyzer and identification of urinary organic acids using Gas Chromatography Mass Spectrometry (GCMS). Patients’ clinical information were obtained from the request forms and case records
Results: Twenty-five patients were diagnosed MSUD. Nineteen patients (76%) were affected by classical MSUD, whereas six patients had non-classical MSUD. Delayed diagnosis was common among our case series, and 80% of patients had survived with treatment with mild-to-moderate learning difficulties.
Conclusion: Our findings suggested that MSUD is not uncommon in Malaysia especially among the Malay and early laboratory diagnosis is crucial.
Competing interests: None declared.
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References
Chuang DT, Shih VE (2001) Maple syrup urine disease (branched-chain ketoaciduria). In: Scriver CR Beaudet AL, Sly WS, Valle D (eds), Childs B, Kinzler KW, Vogelstein B (assoc eds). The Metabolic and Molecular Basis of Inerited Disease, 8th edn. Mc Graw-Hill, New York, pp 1971–2006
Funchal C, Tramontina F, Quincozes dos Santos A, Frage de Souza D, Goncalves CA, Pessoa-Pureur R, Wajner M (2007) Effect of the branched-chain alpha-keto acids accumulating in maple syrup urine disease on S100B release from glial cells. J Neurol Sci 260(1–2):87–94
Gates SC, Sweely CC, Krivit W, Dewitt D, Blaisdell BE (1978) Automated metabolic profiling of organic acids in human urine, II. Analysis of urine samples from healthy adults, sick children and children with neuroblastoma. Clin Chem 24(10):1680–1689
Heldt K, Schwahn B, Marquardt I, Grotzke M, Wendel U (2005) Diagnosis of MSUD by newborn screening allows early intervention without extraneous detoxification. Mol Genet Metab 84(4):313–316
Lee JY, Chiong MA, Estrada SC, Cutingco-De la Paz EM, Silao CLT, Padilla CD (2008) Maple syrup urine disease (MSUD)-Clinical profile of 47 Filipino patients. JIMD Short report #135 Online
Majors RE (1998) Liquid extraction technique for sample preparation. LCGC Asia Pacific 1(2):10–15
Pangkanon S, Charoensiriwatana W, Sangtawesin V (2008) Maple syrup urine disease in Thai infants. J Med Assoc Thai 91(Suppl 3):S41–S44
Pertiwi AKD, Suwaji S, Zabedah MY, Zakiah I (1999) Screening for organic acidurias: method development using capillary gas chromatography with flame ionisation detector (FID) identification. Proceedings for 9th Annual Scientific Meeting of Malaysian Association of Clinical Biochemists
Simon E, Fingerhut R, Baumkötter J, Konstantopoulou V, Ratschmann R, Wendel U (2006) Maple syrup urine disease: favourable effect of early diagnosis by newborn screening on the neonatal course of the disease. J Inherit Metab Dis 29(4):532–537
Tanaka K, Hine DG, West-Dull A, Lynn TB (1980) Gas chromatographic method for analysis of urinary organic acids.1. Retention indices of 155 metabolically important compounds. Clin Chem 16(13):1839–1846
Wappner RS, Gibson KM (2002) Disorders of leucine metabolism. Physician’s guide to the laboratory diagnosis of metabolic disease, 2nd edn. Springer, Berlin, pp 165–189
Yoon HR, Lee KR, Kim H, Kang S, Ha Y, Lee DH (2003) Tandem mass spectrometric analysis for disorders in amino, organic and fatty acid metabolism: two year experience in South Korea. Southeast Asian J Trop Med Public Health 34(Suppl 3):115–120
Acknowledgements
We thank the Director General of Health Malaysia for permission to publish this paper. We would also like to express our gratitude to all Biochemistry staff for their technical assistance and to Dr Zakiah Ismail for initiating the project. Our special thanks to Dr Shahnaz Murad, Director of IMR, Dr. Rohani Md Yasin, Head of Specialized Diagnostic Centre and Dr Mohd Helmi Ismail for critical reading of the manuscript and valuable comments.
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Communicated by: Daniela Karall.
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Yunus, Z.M., Kamaludin, D.A., Mamat, M., Choy, Y.S., Ngu, L. (2011). Clinical and Biochemical Profiles of Maple Syrup Urine Disease in Malaysian Children. In: JIMD Reports - Case and Research Reports, 2012/2. JIMD Reports, vol 5. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_105
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DOI: https://doi.org/10.1007/8904_2011_105
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