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, Eva Morava, Ron A Wevers

Index: Biochim. Biophys. Acta 1802(11) , 1028-35, (2010)

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Abstract

Sedoheptulose, arabitol, ribitol, and erythritol have been identified as key diagnostic metabolites in TALDO deficiency.Urine from 6 TALDO-deficient patients and TALDO-deficient knock-out mice were analyzed using ¹H-NMR spectroscopy and GC-mass spectrometry.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.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.Copyright © 2010 Elsevier B.V. All rights reserved.