TY - JOUR
T1 - In-vivo brain H1-MR-Spectroscopy identification and quantification of 2-hydroxyglutarate in L-2-Hydroxyglutaric aciduria
AU - Anghileri, Elena
AU - Bertolino, Nicola
AU - Salsano, Ettore
AU - Antelmi, Luigi
AU - Carpinelli, Patrizia
AU - Castellotti, Barbara
AU - Zucca, Ileana
AU - Gellera, Cinzia
AU - Bisogno, Raffaele
AU - Caccia, Claudio
AU - Cuccarini, Valeria
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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 methods We 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. Results 2HG 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. Conclusions Brain 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.
AB - 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 methods We 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. Results 2HG 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. Conclusions Brain 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.
KW - 2-hydroxyglutarate (2HG)
KW - 2-Hydroxyglutaric Aciduria (L2HGA)
KW - Brain H-MRS
KW - L2HGA gene
KW - Mass spectrometric methods
KW - Point Resolved Sequence (PRESS)
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U2 - 10.1016/j.brainres.2016.08.013
DO - 10.1016/j.brainres.2016.08.013
M3 - Article
AN - SCOPUS:84983469092
VL - 1648
SP - 506
EP - 511
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -