Research reportIn-vivo brain H1-MR-Spectroscopy identification and quantification of 2-hydroxyglutarate in L-2-Hydroxyglutaric aciduria

- 2-hydroxyglutarate is detected by brain MRS in L-2-Hydroxyglutaric aciduria (L2HGA).
- L2HGA patients show high levels of blood 2-hydroxyglutarate.
- Novel L2HGDH gene mutations are found in all three patients.

L-2-Hydroxyglutaric aciduria (L2HGA) is an extremely rare hereditary neurometabolic disease, characterized by increased L-2-hydroxyglutarate (L2HG) levels in the brain and biological fluids. 24-h urine 2HG level remains the biochemical hallmark for the diagnosis of L2HGA, whereas it is unknown the feasibility to measure in vivo the intracerebral levels of 2HG by using magnetic resonance spectroscopy (MRS).Patients and methodsWe used at 3T H1-MRS Single-Voxel (SV) PRESS sequences tailored to detect 2HG, in three adult patients with the diagnosis of L2HGA and in healthy controls. We also used mass spectrometric methods to measure the levels of 2HG in plasma and serum.Results2HG peak was detected and quantified in the white matter (WM) of the three L2HGA patients, while it was absent in controls. All patients showed also high levels of 2HG in plasma and serum.ConclusionsBrain 2HG detected by MRS may play a role in the diagnosis and follow-up of L2HGA, besides circulating plasma/serum 2HG levels by mass spectrometric assays, although studies on a large cohort of patients are required to confirm these observations.