Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency

Udo F.H. Engelke, Fokje S.M. Zijlstra, Fanny Mochel, Vassili Valayannopoulos, Daniel Rabier, Leo A.J. Kluijtmans, András Perl, Nanda M. Verhoeven-Duif, Pascale de Lonlay, Mirjam M.C. Wamelink, Cornelis Jakobs, Éva Morava, Ron A. Wevers

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background: Sedoheptulose, arabitol, ribitol, and erythritol have been identified as key diagnostic metabolites in TALDO deficiency. Method: Urine from 6 TALDO-deficient patients and TALDO-deficient knock-out mice were analyzed using 1H-NMR spectroscopy and GC-mass spectrometry. Results: Our data confirm the known metabolic characteristics in TALDO-deficient patients. The β-furanose form was the major sedoheptulose anomer in TALDO-deficient patients. Erythronic acid was identified as a major abnormal metabolite in all patients and in knock-out TALDO mice implicating an as yet unknown biochemical pathway in this disease. A putative sequence of enzymatic reactions leading to the formation of erythronic acid is presented. The urinary concentration of the citric acid cycle intermediates 2-oxoglutaric acid and fumaric acid was increased in the majority of TALDO-deficient patients but not in the knock-out mice. Conclusion: Erythronic acid is a novel and major hallmark in TALDO deficiency. The pathway leading to its production may play a role in healthy humans as well. In TALDO-deficient patients, there is an increased flux through this pathway. The finding of increased citric acid cycle intermediates hints toward a disturbed mitochondrial metabolism in TALDO deficiency.

Original languageEnglish (US)
Pages (from-to)1028-1035
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1802
Issue number11
DOIs
StatePublished - Nov 1 2010

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Keywords

  • 2-Oxoglutaric acid
  • Citric acid cycle intermediates
  • Erythronic acid
  • NMR spectroscopy
  • Pentose phosphate pathway
  • Polyols
  • Sedoheptulose
  • Transaldolase deficiency

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

Engelke, U. F. H., Zijlstra, F. S. M., Mochel, F., Valayannopoulos, V., Rabier, D., Kluijtmans, L. A. J., Perl, A., Verhoeven-Duif, N. M., de Lonlay, P., Wamelink, M. M. C., Jakobs, C., Morava, É., & Wevers, R. A. (2010). Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1802(11), 1028-1035. https://doi.org/10.1016/j.bbadis.2010.06.007