The effects of copper-histidine therapy on brain metabolism in a patient with Menkes disease: a proton magnetic resonance spectroscopic study.
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.
Munakata
Mitsutoshi
M
Department of Pediatrics, Tohoku University School of Medicine, Sendai 980-8574, Japan. muna@ped.med.tohoku.ac.jp
Sakamoto
Osamu
O
Kitamura
Taro
T
Ishitobi
Mamiko
M
Yokoyama
Hiroyuki
H
Haginoya
Kazuhiro
K
Togashi
Noriko
N
Tamura
Hajime
H
Higano
Shuichi
S
Takahashi
Shoki
S
Ohura
Toshihiro
T
Kobayashi
Yasuko
Y
Onuma
Akira
A
Iinuma
Kazuie
K
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
D009942:Organometallic Compounds; D011522:Protons; D006639:Histidine; D003300:Copper; C098468:copper histidine; D002570:Ceruloplasmin