Journal of Inherited Metabolic Disease

, Volume 22, Issue 2, pp 107–114

4,5-Dimethyl-3-hydroxy-2[5H]-furanone (sotolone) — The odour of maple syrup urine disease

  • F. Podebrad
  • M. Heil
  • S. Reichert
  • A. Mosandl
  • A. C. Sewell
  • H. Böhles
Article

Abstract

Maple syrup urine disease is an autosomal recessive inherited disorder of branched-chain amino acid metabolism due to deficiency of the branched-chain α-keto acid dehydrogenase complex. The disease was originally named after the characteristic sweet aroma, reminiscent of maple syrup, present in the body fluids of affected patients. Until now, the substance responsible for the odour has not been positively identified. Using enantioselective multidimensional gas chromatography-mass spectrometry (enantio-MDGC-MS), we could demonstrate that 4,5-dimethyl-3-hydroxy-2[5H]-furanone (sotolone), a well-known flavour impact compound present in fenugreek and lovage, was present in urine from seven patients with maple syrup urine disease. Urine samples from healthy control persons lacked sotolone. We have shown that sotolone is responsible for the characteristic odour of maple syrup urine disease and, since maple syrup also contains sotolone, the naming of this disease appears to be correct.

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REFERENCES

  1. Alcock NW, Crout DHG, Gregorio MVM, Lee E, Pike G, Samuel CJ (1989) Stereochemistry of the 4-hydroxyisoleucine from Trigonella foenum-graecum. Phytochemistry 28: 1835-1841.Google Scholar
  2. Bartley GB, Hilty MD, Anderson BD, Clairmont AC, Maschke SP (1981) `Maple syrup' urine odor due to fenugreek ingestion. N Engl J Med 305: 467.Google Scholar
  3. Bauer K, Garbe D, Surburg H (1997) Common Fragrance and Flavor Materials: Preparation Properties and Uses, 3rd edn. Weinheim: Wiley-VCH, 149.Google Scholar
  4. Belford AL, Lindsay RC, Ridley SC (1991) Contributions of selected flavor compounds to the sensory properties of maple syrup. J Sens Stud 6: 101-118.Google Scholar
  5. Bruche G (1993) Stereodifferenzierung und herkunftsspeziÐsche Analyse aromarelevanter Dihydrofuranone. Doctoral Thesis, University of Frankfurt. J. Inher. Metab. Dis. 22 (1999)Google Scholar
  6. Burke DG, Halpern B, Malegan D, et al (1983) Profiles of urinary volatiles from metabolic disorders. Clin Chem 29: 1834-1838.Google Scholar
  7. Carpenter DG, Carter CH (1970) Inborn errors of metabolism associated with unusual odors. J Florida Med Assoc 57: 31-33.Google Scholar
  8. Chuang DT, Shih VE (1995) Disorders of branched-chain amino acid and keto acid metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease, 7th edn. New York: McGraw-Hill, 1239-1277.Google Scholar
  9. Cone TE (1968) Diagnosis and treatment: some diseases, syndromes and conditions associated with an unusual odor. Pediatrics 41: 993-995.Google Scholar
  10. Dietrich A, Mass B, Messer W, et al (1992) Stereoisomeric flavour compounds. Part LVIII: The use of heptakis (2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-b-cyclodextrin as a chiral stationary phase in flavour analysis. J High Resolut Chromatogr 15: 590-593.Google Scholar
  11. Fowden L, Pratt HM, Smith A (1973) 4-Hydroxyisoleucine from seed of Trigonella foenumgraecum. Phytochemistry 12: 1707-1711.Google Scholar
  12. Hauser GJ, Chitayat D, Berns L, Braver D, Mauhlbauer B (1985) Peculiar odours in newborns and maternal prenatal ingestion of spicy food. Eur J Pediatr 144: 403.Google Scholar
  13. Hofmann T, Schieberle P (1997) Studies on the formation of the intense flavour compounds 2-methyl-3-furanthiol, 2-acetyl-2-thiazoline and sotolone in cysteine/carbohydrate mixtures. Deutsche Forschungsanstalt Lebensmittelchemie (DFA) Bericht, Garching, October für 1997, 66-73.Google Scholar
  14. Menkes JH (1959) Maple syrup urine disease-investigations into the metabolic defect. Neurology 9: 826-835.Google Scholar
  15. Menkes JH, Hurst PL, Craig JM (1954) A new syndrome: progressive familial infantile cerebral dysfunction associated with an unusual urinary substance. Pediatrics 14: 462-466.Google Scholar
  16. Monastiri K, Limame K, Kaabachi N, et al (1997) Fenugreek odour in maple syrup urine disease. J Inher Metab Dis 20: 614-615.Google Scholar
  17. Podebrad F, Heil M, Leib S, Geier B, Beck T, Mosandl A (1997) Analytical approach in diagnosis of inherited metabolic disease: maple syrup urine disease (MSUD)-simultaneous analysis of metabolites in urine by enantioselective multidimensional capillary gas chromatography mass spectrometry (enantio-MDGC-MS). J High Resolut Chromatogr 20: 355-362.Google Scholar
  18. Snyderman SE, Norton PM, Roitman E, Holt LE (1964) Maple syrup urine disease with particular reference to diet therapy. Pediatrics 34: 454-472.Google Scholar
  19. Sulser H, Habegger M, Büchi W (1972) Synthese und Geschmacksprüfung von 3,4-disubstituierten 2-Hydroxy-2-buten-1,4-oliden. Z Lebensm Unters Forsch 148: 215-221.Google Scholar
  20. Yeung CY, Lin SP, Kao HA et al (1993) Maple syrup urine disease: report of two cases. J Formos Med Assoc 92: 765-768.Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • F. Podebrad
    • 1
  • M. Heil
    • 1
  • S. Reichert
    • 1
  • A. Mosandl
    • 1
  • A. C. Sewell
    • 2
  • H. Böhles
    • 2
  1. 1.Institute of Food ChemistryUniversity of FrankfurtFrankfurt am MainGermany
  2. 2.Department of PaediatricsUniversity of FrankfurtFrankfurt am MainGermany

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