Oxidative stress among L-2-hydroxyglutaric aciduria disease patients: evaluation of dynamic thiol/disulfide homeostasis

Metab Brain Dis. 2019 Feb;34(1):283-288. doi: 10.1007/s11011-018-0354-8. Epub 2018 Nov 29.


L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive disorder that is caused by deficiency of 2-hydroxyglutarate dehydrogenase. Pathophysiology of brain damage is poorly understood. In recent years, it was proposed that oxidative stress was elevated and led to brain injury. Aim of this study is to evaluate thiol/disulphide homeostasis as an indicator of oxidative stress in L2HGA patients who have been receiving antioxidant treatment. Sixteen L2HGA patients and 16 healthy individuals were included in the study. All the L2HGA patients were regularly followed up and presented neurological dysfunction at different grades. Fourteen patients had been receiving antioxidant treatment. Serum native thiol (-SH), total thiol (-SH + -S-S-) and disulphide (-S-S) levels were measured. Disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated from these values. No significant difference was observed in -SH, -SH + -S-S-, -S-S levels between two groups. In addition to that, no increase of disulphide/native thiol and disulphide/total thiol ratios was detected. Thiol/disulphide homeostasis parameters were also compared between patients who had been receiving and not receiving antioxidant therapy; and between different types of antioxidant therapy and the results did not point to any significant difference. This is the first study that evaluates dynamic thiol/disulphide homeostasis as an indicator of oxidative stress in L2HGA and it has one of the largest sample sizes among previous studies. In our study we suggest that antioxidant therapy should be effective in preventing oxidative stress in L2HGA patients, which has been reported in previous studies and should be a part of standard therapy.

Keywords: L2HGA; Neurotoxicity; Oxidative stress; Thiol/disulphide homeostasis.

MeSH terms

  • Adolescent
  • Adult
  • Brain Diseases, Metabolic, Inborn / metabolism*
  • Child
  • Child, Preschool
  • Disulfides / blood*
  • Female
  • Homeostasis / physiology*
  • Humans
  • Male
  • Oxidative Stress / physiology*
  • Prospective Studies
  • Sulfhydryl Compounds / blood*
  • Young Adult


  • Disulfides
  • Sulfhydryl Compounds

Supplementary concepts

  • 2-Hydroxyglutaricaciduria