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Disorders of Fructose Metabolism

  • Chapter
Inborn Metabolic Diseases

Zusammenfassung

Three inborn errors are known in the pathway of fructose metabolism. Essential fructosuria is a harmless anomaly characterised by the appearance of fructose in the urine after the intake of fructose-containing food. In hereditary fructose intolerance (HFI), fructose may provoke prompt gastrointestinal discomfort and hypoglycaemia upon ingestion, symptoms that can vary from patient to patient and depend on the ingested dose. Fructose may cause liver and kidney failure when taken persistently, and its intake becomes life-threatening when given intravenously. Fructose-1,6-bisphosphatase (FBPase) deficiency is also usually considered an inborn error of fructose metabolism although, strictly speaking, it is a defect of gluconeogenesis. The disorder is manifested by the appearance of hypoglycaemia and lactic acidosis (neonatally, or later during fasting or induced by fructose) and may be life-threatening

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References

  1. Cox TM (2002) The genetic consequences of our sweet tooth. Nat Rev Genet 3:481–487

    Google Scholar 

  2. Asipu A, Hayward BE, O’Reilly J, Bonthron DT (2003) Properties of normal and mutant recombinant human ketohexokinases and implications for the pathogenesis of essential fructosuria. Diabetes 52:2426–2432

    Google Scholar 

  3. Bonthron DT, Brady N, Donaldson IA, Steinmann B (1994) Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase). Hum Mol Genet 3:1627–1631

    Google Scholar 

  4. Trinh CH, Asipu A, Bonthron DT, Phillips SE (2009) Structures of alternatively spliced isoforms of human ketohexokinase. Acta Crystallogr D Biol Crystallogr 65:201–211

    Google Scholar 

  5. Boesiger P, Buchli R, Meier D, Steinmann B, Gitzelmann R (1994) Changes of liver metabolite concentrations in adults with disorders of fructose metabolism after intravenous fructose by 31P magnetic resonance spectroscopy. Pediatr Res 36:436–440

    Google Scholar 

  6. Chambers RA, Pratt RT (1956) Idiosyncrasy to fructose. Lancet 271:340

    Google Scholar 

  7. Froesch ER, Prader A, Labhart A, Stuber HW, Wolf HP (1957) Die hereditäre Fructoseintoleranz, eine bisher nicht bekannte kongenitale Stoffwechselstörung. Schweiz Med Wochenschr 87:1168–1171

    Google Scholar 

  8. Baerlocher K, Gitzelmann R, Steinmann B, Gitzelmann-Cumarasamy N (1978) Hereditary fructose intolerance in early childhood: a major diagnostic challenge. Survey of 20 symptomatic cases. Helv Paediatr Acta 33:465–487

    Google Scholar 

  9. Mock DM, Perman JA, Thaler MM, Morris RC Jr (1983) Chronic fructose intoxication after infancy in children with hereditary fructose intolerance. A cause of growth retardation. N Engl J Med 309:764–770

    Google Scholar 

  10. Lameire N, Mussche M, Baele G, Kint J, Ringoir S (1978) Hereditary fructose intolerance: a difficult diagnosis in the adult. Am J Med 65:416–423

    Google Scholar 

  11. Van den Berghe G (1978) Metabolic effects of fructose in the liver. Curr Top Cell Regul 13:97–135

    Google Scholar 

  12. Jaeken J, Pirard M, Adamowicz M, Pronicka E, Van Schaftingen E (1996) Inhibition of phosphomannose isomerase by fructose-1-phosphate: an explanation for defective N-glycosylation in hereditary fructose intolerance. Pediatr Res 40:764–766

    Google Scholar 

  13. Woods HF, Alberti KGMM (1972) Dangers of intravenous fructose. Lancet II:1354–1357

    Google Scholar 

  14. Cross NCP, de Franchis R, Sebastio G et al. (1990) Molecular analysis of aldolase B genes in hereditary fructose intolerance. Lancet 335:306–309

    Google Scholar 

  15. Santer R, Rischewski J, von Weihe M et al. (2005) The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe. Hum Mutat 25:594

    Google Scholar 

  16. Davit-Spraul A, Costa C, Zater M et al. (2008) Hereditary fructose intolerance: frequency and spectrum mutations of the aldolase B gene in a large patients cohort from France – identification of eight new mutations. Mol Genet Metab 94:443–447

    Google Scholar 

  17. Steinmann B, Gitzelmann R (1981) The diagnosis of hereditary fructose intolerance. Helv Paediatr Acta 36:297–316

    Google Scholar 

  18. Gibson PR, Newnham E, Barrett JS, Shepherd SJ, Muir JG (2007) Fructose malabsorption and the bigger picture. Aliment Pharmacol Ther 25:349–363

    Google Scholar 

  19. Müller P, Meier C, Böhme HJ, Richter T (2003) Fructose breath hydrogen test – is it really a harmless diagnostic procedure? Dig Dis 21:276–278

    Google Scholar 

  20. Commission Directive of 14 May 1991 on infant formulae and follow-on formulae (91/321/EEC) (1991) No L 175/35–51

    Google Scholar 

  21. Odièvre M, Gentil C, Gautier M, Alagille D (1978) Hereditary fructose intolerance in childhood. Diagnosis, management and course in 55 patients. Am J Dis Child 132:605–608

    Google Scholar 

  22. Baker L, Winegrad AI (1970) Fasting hypoglycemia and metabolic acidosis associated with deficiency of hepatic fructose-1,6-bisphosphatase activity. Lancet II:13–16

    Google Scholar 

  23. Åsberg C, Hjalmarson O, Alm J et al. (2010) Fructose 1,6-bisphosphatase deficiency: enzyme and mutation analysis performed on calcitriol-stimulated monocytes with a note on long-term prognosis. J Inherit Metab Dis 33:178

    Google Scholar 

  24. Afroze B, Yunus Z, Steinmann B, Santer R (2013) Transient pseudo-hypertriglyceridemia: a useful biochemical marker of fructose- 1,6-bisphosphatase deficiency. Eur J Pediatr 172:1249–1253

    Google Scholar 

  25. Morris AA, Deshphande S, Ward-Platt MP et al. (1995) Impaired ketogenesis in fructose-1,6-bisphosphatase deficiency: a pitfall in the investigation of hypoglycemia. J Inherit Metab Dis 18:28–32

    Google Scholar 

  26. Huidekoper HH, Visser G, Ackermans MT, Sauerwein HP, Wijburg FA (2010) A potential role for muscle in glucose homeostasis: in vivo kinetic studies in glycogen storage disease type 1a and fructose-1,6-bisphosphatase deficiency. J Inherit Metab Dis 33:25–31

    Google Scholar 

  27. Baerlocher K, Gitzelmann R, Nüssli R, Dumermuth G (1971) Infantile lactic acidosis due to hereditary fructose 1,6-diphosphatase deficiency. Helv Paediatr Acta 26:489–506

    Google Scholar 

  28. Santer R, du Moulin M, Shahinyan T et al. (2016) A summary of molecular genetic findings in fructose-1,6-bisphosphatase deficiency with focus on a common long-range deletion and the role of MLPA analysis. Orphanet J Rare Dis 11:44–50

    Google Scholar 

  29. Kikawa Y, Inuzuka M, Jin BY et al. (1997) Identification of genetic mutations in Japanese patients with fructose-1,6-bisphosphatase deficiency. Am J Hum Genet 61:852–861

    Google Scholar 

  30. Herzog B, Morris AA, Saunders C, Eschrich K (2001) Mutation spectrum in patients with fructose-1,6-bisphosphatase deficiency. J Inherit Metab Dis 24:87–88

    Google Scholar 

  31. Hers HG, Van Schaftingen E (1982) Fructose 2,6-bisphosphate two years after its discovery. Biochem J 206:1–12

    Google Scholar 

  32. Besley GTN, Walter JH, Lewis MA, Chard CR, Addison GM (1994) Fructose-1,6-bisphosphatase deficiency: severe phenotype with normal leukocyte enzyme activity. J Inherit Metab Dis 17:333–335

    Google Scholar 

  33. Hasegawa Y, Kikawa Y, Miyamaoto J et al. (2003) Intravenous glycerol therapy should not be used in patients with unrecognized fructose-1,6-bisphosphatase deficiency. Pediatr Int 45:5–9

    Google Scholar 

  34. Krishnamurthy V, Eschrich K, Boney A et al. (2007) Three successful pregnancies through dietary management of fructose-1,6-bisphosphatase deficiency. J Inherit Metab Dis 30:819

    Google Scholar 

  35. Sugita G, Tsuyoshi H, Nishijima K, Yoshida Y (2014) Fructose-1,6-bisphosphatase deficiency: a case of a successful pregnancy by closely monitoring metabolic control. JIMD Rep 14:115–118

    Google Scholar 

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Authors and Affiliations

  1. Division of Metabolism, University Children’s Hospital, Steinwiesstrasse 75, 8032, Zürich, Switzerland

    Beat Steinmann

  2. Department of Pediatrics, University Medical Centre Hamburg Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    René Santer

Authors
  1. Beat Steinmann
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  2. René Santer
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Correspondence to Beat Steinmann or René Santer .

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Editors and Affiliations

  1. Department of Neurology, Neurometabolic Unit, Hôpital Pitié Salpêtrière, Paris, France

    Jean-Marie Saudubray

  2. Division of Metabolism, University Children’s Hospital, Zurich, Switzerland

    Matthias R. Baumgartner

  3. Willink Biochemical Genetics Unit Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK

    John Walter

  4. Central Manchester University Hospitals NHS Foundation Trust, St Mary‘s Hospital, Manchester, UK

    John Walter

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Steinmann, B., Santer, R. (2016). Disorders of Fructose Metabolism. In: Saudubray, JM., Baumgartner, M., Walter, J. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-49771-5_8

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  • DOI: https://doi.org/10.1007/978-3-662-49771-5_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-49769-2

  • Online ISBN: 978-3-662-49771-5

  • eBook Packages: MedicineMedicine (R0)

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