Tel: 1-631-626-9181 (USA)   44-207-097-1828 (Europe)


Our promise to you:
Guaranteed product quality, expert customer support.



Bookmark and Share
Official Full Name
L-2-hydroxyglutarate dehydrogenase
This gene encodes L-2-hydroxyglutarate dehydrogenase, a FAD-dependent enzyme that oxidizes L-2-hydroxyglutarate to alpha-ketoglutarate in a variety of mammalian tissues. Mutations in this gene cause L-2-hydroxyglutaric aciduria, a rare autosomal recessive neurometabolic disorder resulting in moderate to severe mental retardation.
L2HGDH; L-2-hydroxyglutarate dehydrogenase; C14orf160, chromosome 14 open reading frame 160; L-2-hydroxyglutarate dehydrogenase, mitochondrial; 2 hydroxyglutarate dehydrogenase; FLJ12618; mitochondrial; C14orf160; Duranin; L2HDH_HUMAN; OTTHUMP00000178967; OTTHUMP00000178968; OTTHUMP00000244606; alpha-ketoglutarate reductase; 2-hydroxyglutarate dehydrogenase; alpha-hydroxyglutarate oxidoreductase; L-alpha-hydroxyglutarate dehydrogenase; si:ch211-67f24.10

Recent Progress

L-2-hydroxyglutarate dehydrogenase is a mitochondrial enzyme in humans that is encoded by the L2HGDH gene on chromosome 14. This protein is a spotlight for research because of its clinical significance. Mutations in the L2HGDH gene cause L-2-hydroxyglutaric aciduria, which is a rare autosomal recessive neuro-metabolic disorder. Toxic accumulation of high concentration of L-2-hydroxyglutaric acid in the plasma and cerebrospinal fluid are discovered in individuals with L2HGDH mutations.

Moreover, researcher has discovered that patients with L-2-hydroxyglutaric aciduria (L2HGA) also present neurological symptoms and characteristic neuro-radiological findings, especially subcortical white matter abnormalities. After adopting the genotype-first approach of the whole exome sequence, compound heterozygous mutations of L2HGDH was discovered. The sample investigated was an adult patient with intellectual disability and epilepsy. A retrospective assay was also used to prove the concentrations of 2-hydroxyglutaric acid in the urine did increase. These findings taken together indicated that neuro-radiological findings of subcortical white matter abnormalities are features of L2HGA(the disease caused by abnormality in L2HGDH), moreover, clinical exome sequencing plays a role in compensating for insufficient clinical evaluations.

Researcher also studied that whether L-2-HGA could provoke DNA oxidative damage in blood leukocytes and whether L-carnitine (LC) could prevent this kind of in vitro DNA damage. Researcher discovered that a certain amount (30 μM) of L-2-HG significantly induced DNA damage. However, this kind of damage is effectively prevented by 30 and 150 μM of LC. Oxidative stress parameters in urine of L-2-HGA patients were also observed. Investigator discovered that oxidized guanine species and di-tyrosine increase significantly. This indicated increase in oxidative DNA and protein damage. This data again proved that the presence of oxidative damage on DNA and protein in patients is affected by these diseases, and LC can prevent that from happening.

In order to test the feasibility to measure in vivo the intracerebral levels of 2HG by using magnetic resonance spectroscopy (MRS), researcher used at 3T H 1-MRS Single-Voxel (SV) PRESS sequences tailored to detect 2HG, in three adult patients with the diagnosis of L2HGA along with healthy controls. These findings suggest that brain 2HG using MRS can play a role in the diagnosis and follow-up of L2HGA, additional to circulating plasma/serum 2HG levels by mass spectrometric assays.

Investigator produced L2HGDH knockout (KO) mice and observed a considerable increase of L-2-hydroxyglutarate (L-2-HG) levels in multiple tissues. The highest levels of L-2-HG appeared in the brain and testis, coupled with an increase in histone methylation in these tissues. White matter abnormalities, extensive gliosis, microglia-mediated neuro-inflammation, along with an expansion of oligodendrocyte progenitor cells (OPCs) were also discovered in L2HGDH KO mice. What’s more, impairment of adult hippocampal neurogenesis and late-onset neurodegeneration in mouse brains has also been linked with L2HGDH. These data provide in vivo evidence that L2HGDH mutation leads to L-2-HG accumulation, leukoencephalopathy, and neurodegeneration in mice, offering new thoughts into the pathophysiology of L-2-HGA in humans.

Using a metabolomics approach, researcher was able to identify elevations of the metabolite 2- hydroxyglutarate (2-HG) in the most common histology of kidney cancer, among the most common malignancies in both men and women. After adopting subsequent analysis, the predominant enantiomer of 2-HG elevated in renal cancer was proved to be the L(S) form. Increase of L-2HG are considered due in part to loss of expression of the L2HGDH. These findings suggest that metabolites may play a role in tumor development and/or progression, which is similarly to oncogenes and oncoproteins. 


  1. Yamamoto, Toshiyuki, et al. "White matter abnormalities in an adult patient with l-2-hydroxyglutaric aciduria.." Brain & Development 38.1 (2016): 142-144.
  2. Rodrigues, Daiane Grigolo Bardemaker, et al. "Experimental evidence of oxidative stress in patients with l-2-hydroxyglutaric aciduria and that l-carnitine attenuates in vitro DNA damage caused by d-2-hydroxyglutaric and l-2-hydroxyglutaric acids." Toxicology in Vitro (2017): 47-53.
  3. Anghileri, Elena, et al. "In-vivo brain H1-MR-Spectroscopy identification and quantification of 2-hydroxyglutarate in L-2-Hydroxyglutaric aciduria." Brain Research (2016): 506-511.
  4. Ma, Shenghong, et al. "L2hgdh Deficiency Accumulates l-2-Hydroxyglutarate with Progressive Leukoencephalopathy and Neurodegeneration." Molecular and Cellular Biology 37.8 (2017).
  5. Shim, Eunhee, et al. "l-2-Hydroxyglutarate: An Epigenetic Modifier and Putative Oncometabolite in Renal Cancer." Cancer Discovery 4.11 (2014): 1290-1298.