title: Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency.
abstract: BACKGROUND
  Sedoheptulose, arabitol, ribitol, and erythritol have been identified as key diagnostic metabolites in TALDO deficiency.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Radboud University Nijmegen Medical Centre, Department of Laboratory Medicine, Laboratory of Genetic Endocrine and Metabolic Diseases, Nijmegen, The Netherlands. u.engelke@labgk.umcn.nl
authors.forename: Udo F H
authors.initials: UF
authors.lastname: Engelke
authors.forename: Fokje S M
authors.initials: FS
authors.lastname: Zijlstra
authors.forename: Fanny
authors.initials: F
authors.lastname: Mochel
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.forename: Daniel
authors.initials: D
authors.lastname: Rabier
authors.forename: Leo A J
authors.initials: LA
authors.lastname: Kluijtmans
authors.forename: András
authors.initials: A
authors.lastname: Perl
authors.forename: Nanda M
authors.initials: NM
authors.lastname: Verhoeven-Duif
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
authors.forename: Mirjam M C
authors.initials: MM
authors.lastname: Wamelink
authors.forename: Cornelis
authors.initials: C
authors.lastname: Jakobs
authors.forename: Eva
authors.initials: E
authors.lastname: Morava
authors.forename: Ron A
authors.initials: RA
authors.lastname: Wevers
mesh_terms: D000293:Adolescent; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D002087:Butyrates / Q000737:chemistry / Q000652:urine*; D002675:Child, Preschool; D005650:Fumarates / Q000737:chemistry / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D006539:Heptoses / Q000737:chemistry / Q000652:urine; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007656:Ketoglutaric Acids / Q000737:chemistry / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D015394:Molecular Structure; D010427:Pentose Phosphate Pathway; D012255:Ribitol / Q000737:chemistry / Q000652:urine; D013402:Sugar Alcohols / Q000737:chemistry / Q000652:urine; D014153:Transaldolase / Q000172:deficiency* / Q000235:genetics
chemical_list: D015415:Biomarkers; D002087:Butyrates; D005650:Fumarates; D006539:Heptoses; D007656:Ketoglutaric Acids; D013402:Sugar Alcohols; C121691:erythronic acid; C003011:sedoheptulose; D012255:Ribitol; C032005:fumaric acid; D014153:Transaldolase; C014999:arabitol