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

作者：Engelke Udo F H^*; Zijlstra Fokje S M; Mochel Fanny; Valayannopoulos Vassili; Rabier Daniel; Kluijtmans Leo A J; Perl Andras; Verhoeven Duif Nanda M; de Lonlay Pascale; Wamelink Mirjam M C; Jakobs Cornelis; Morava Eva; Wevers Ron A

来源：Biochimica et Biophysica Acta-Molecular Basis of Disease, 2010, 1802(11): 1028-1035.

DOI：10.1016/j.bbadis.2010.06.007

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

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 (1)H-NMR spectroscopy and GC-mass spectrometry Results: Our data confirm the known metabolic characteristics in TALDO-deficient patients The p-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 cam 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.

• 出版日期2010-11