Novel insights into L-2-hydroxyglutaric aciduria: Mass isotopomer studies reveal 2-oxoglutaric acid as the metabolic precursor of L-2-hydroxyglutaric acid

Original Article


Employing lymphoblasts derived from two non related patients with l-2-HG aciduria, we examined the origin of l-2-hydroxyglutaric acid (l-2-HG) through incubation with [13C6]glucose and [2H5]glutamic acid. Formation of labelled 2-ketoglutaric acid (2-KG), citric acid and l-2-HG was determined by GC-MS. The quantitative and qualitative isotopomer pattern following incubation with [13C6]glucose was identical for all end-products. Incubations with [2H5]glutamic acid as precursor revealed the formation of identical isotopomers for 2-KG and l-2-HG. Our data indicate that 2-KG is the metabolic precursor of l-2-HG, adding to previous studies which revealed that 2-KG is the metabolic precursor of d-2-HG. These data suggest that 2-KG has a pathophysiological role in combined d/l-2-HG aciduria.


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Copyright information

© SSIEM and Springer 2007

Authors and Affiliations

  1. 1.VU University Medical CentreClinical ChemistryAmsterdamThe Netherlands
  2. 2.Biochemical Genetics Laboratory, Children’s Hospital Pittsburgh, Departments of Pediatrics, Pathology and Human Genetics, Division of Medical GeneticsUniversity of Pittsburgh School of MedicinePittsburghUSA

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