title: In-vivo brain H1-MR-Spectroscopy identification and quantification of 2-hydroxyglutarate in L-2-Hydroxyglutaric aciduria.
abstract: 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).
  
  
  
  We used at 3T H(1)-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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milano, Italy. Electronic address: elena.anghileri@istituto-besta.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Anghileri
authors.affiliation: Scientific Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Bertolino
authors.affiliation: Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Salsano
authors.affiliation: Health Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Antelmi
authors.affiliation: Biology Department, Nerviano Medical Sciences S.r.l., Nerviano, Milano, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Carpinelli
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Castellotti
authors.affiliation: Scientific Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Ileana
authors.initials: I
authors.lastname: Zucca
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Gellera
authors.affiliation: Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; University of Milan, Via Festa del Perdono 7, Milano, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Bisogno
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Caccia
authors.affiliation: Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cuccarini
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D020739:Brain Diseases, Metabolic, Inborn / Q000097:blood / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D005977:Glutarates / Q000097:blood / Q000378:metabolism* / Q000652:urine; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005977:Glutarates; C019417:alpha-hydroxyglutarate
keywords: 2-Hydroxyglutaric Aciduria (L2HGA); 2-hydroxyglutarate (2HG); Brain H(1)-MRS; L2HGA gene; Mass spectrometric methods; Point Resolved Sequence (PRESS)