title: The effects of copper-histidine therapy on brain metabolism in a patient with Menkes disease: a proton magnetic resonance spectroscopic study.
abstract: We report on metabolic changes in the brain of a boy with Menkes disease. He was treated with parenteral copper (Cu)-histidine supplementation, from 5 months of age, and assessed with proton magnetic resonance spectroscopy ((1)H-MRS). The single-voxel (1)H-MRS before treatment revealed an accumulation of lactate and a reduced N-acetyl aspartate (NAA)/total creatine (tCr) ratio with a z-score of -3.0. During treatment, the lactate signal faded away, whereas the NAA signal gradually increased to a z-score of -1.5 at 120 days of treatment. The choline/tCr ratio did not deviate much initially (z-score +0.5), but the ratio increased markedly during treatment (z-score +4.8). Consequently, the Cu-histidine therapy initiated after the critical period still improved the neuronal metabolism, suggesting that some Cu was delivered to neurons. Nevertheless, the brain atrophy, impaired myelination, and severe neurological symptoms were not ameliorated.
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai 980-8574, Japan. muna@ped.med.tohoku.ac.jp
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Munakata
authors.forename: Osamu
authors.initials: O
authors.lastname: Sakamoto
authors.forename: Taro
authors.initials: T
authors.lastname: Kitamura
authors.forename: Mamiko
authors.initials: M
authors.lastname: Ishitobi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Haginoya
authors.forename: Noriko
authors.initials: N
authors.lastname: Togashi
authors.forename: Hajime
authors.initials: H
authors.lastname: Tamura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Higano
authors.forename: Shoki
authors.initials: S
authors.lastname: Takahashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ohura
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Onuma
authors.forename: Kazuie
authors.initials: K
authors.lastname: Iinuma
mesh_terms: D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002570:Ceruloplasmin / Q000032:analysis; D003300:Copper / Q000097:blood; D006639:Histidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000627:therapeutic use*; D011522:Protons
chemical_list: D009942:Organometallic Compounds; D011522:Protons; D006639:Histidine; D003300:Copper; C098468:copper histidine; D002570:Ceruloplasmin