Case report| Volume 27, ISSUE 4, P297-300, June 2005

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 (1H-MRS). The single-voxel 1H-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.


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        • Menkes J.H.
        Kinky hair disease: twenty five years later.
        Brain Dev. 1988; 10: 77-79
        • Kodama H.
        • Murata Y.
        Molecular genetics and pathophysiology of Menkes disease.
        Pediatr Int. 1999; 41: 430-435
        • Castillo M.
        • Kwock L.
        • Mukherji S.K.
        Clinical applications of proton MR spectroscopy.
        Am J Neuroradiol. 1996; 17: 1-15
        • Tsurui S.
        • Sugie H.
        A pathophysiological study of macular mutant mouse as a model of human Menkes kinky hair disease.
        II. Analysis of brain metabolism using 31P- and 1H-nuclear magnetic resonance spectroscopy (in Japanese). No To Hattatsu (Tokyo). 1990; 22: 566-572
        • Morgello S.
        • Peterson H.D.
        • Kahn L.J.
        • Laufer H.
        Menkes kinky hair disease with ‘ragged red’ fibers.
        Dev Med Child Neurol. 1988; 30: 812-816
        • Yoshimura N.
        • Kudo H.
        Mitochondrial abnormalities in Menkes' kinky hair disease (MKHD).
        Electron-microscopic study of the brain from an autopsy case. Acta Neuropathol (Berl). 1983; 59: 295-303
        • Pouwels P.J.
        • Brockmann K.
        • Kruse B.
        • Wilken B.
        • Wick M.
        • Hanefeld F.
        • Frahm J.
        Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS.
        Pediatr Res. 1999; 46: 474-485
        • Barnard R.O.
        • Best P.V.
        • Erdohazi M.
        Neuropathology of Menkes' disease.
        Dev Med Child Neurol. 1978; 20: 586-597
        • Kodama H.
        Recent developments in Menkes disease.
        J Inherit Metab Dis. 1993; 16: 791-799
        • Rossi L.
        • De Martino A.
        • Marchese E.
        • Piccirilli S.
        • Rotilio G.
        • Ciriolo M.R.
        Neurodegeneration in the animal model of Menkes' disease involves Bcl-2-linked apoptosis.
        Neuroscience. 2001; 103: 181-188