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Clinical and biochemical consequences of copper-histidine therapy in Menkes disease

  • Metabolic Diseases
  • Published:
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Abstract

Menkes disease (MD) is an X-linked recessively inherited neurodegenerative disorder of copper (Cu) metabolism leading to death in early childhood. Symptoms are attributed to deficient activity of Cu-dependent enzymes. Limited experience has been reported concerning clinical and biochemical consequences of parenteral treatment with copper-(histidine)2-complex (Cu-His) in MD. Cu-His was administered in a 13-week-old boy with MD by daily intramuscular injections. After 6 weeks of therapy, Cu and caeruloplasmin in serum and Cu in CSF were normalized. The excessive dopamine level in CSF was corrected after 3 months of treatment. After 6 weeks of Cu supplementation, complete reduction of epileptic discharges, improved muscular tone and increased motor activities were observed. Developmental regression stopped and was replaced by a slight progression. Death at the age of 19 months was caused by septicaemia due to a fulminant urinary tract infection; there was no evidence of chronic Cu toxicity. These findings suggest that Cu-His supplementation may be a promising palliative treatment in MD.

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Abbreviations

Cu-His:

copper-(histidine)2-complex

MD:

Menkes disease

References

  1. Adams PC, Strand RD, Bresnan MJ, Lucky AW (1974) Kinky hair syndrome: serial study of radiological findings with emphasis on the similarity to the battered child syndrom. Radiology 112:401–407

    PubMed  Google Scholar 

  2. Baerlocher K, Nadal D (1988) Das Menkes-Syndrom. Ergeb Inn Med Kinderheilkd 57:79–144

    Google Scholar 

  3. Barnea A, Katz BM (1990) Uptake of67copper complexed to3H-histidine by brain hypothalamic slices: evidence that dissociation of the complex is not the only factor determining67copper uptake. J Inorg Biochem 40:81–93

    PubMed  Google Scholar 

  4. Barnea A, Hartter DE, Cho G, Bhasker KR, Katz BM, Edwards MD (1990) Further characterization of the process of in vitro uptake of radiolabeled copper by the rat brain. J Inorg Biochem 40:103–110

    PubMed  Google Scholar 

  5. Butler IJ, Seifert WE, Koslow SH, Caprioli RM, Singer HS (1979) Neurotransmitters in neurological disorders of childhood. In: Usdin B, Kopin IJ, Barchap J (eds) Proceedings of the Fourth International Catecholamine Symposium. Pergamon, New York, pp 1578–1580

    Google Scholar 

  6. Chelly J, Tümer Z, Tønnesen T, Petterson A, Ishikawa-Brush Y, Tommerup N, Horn N, Monaco AP (1993) Isolation of a candidate gene for Menkes disease that encodes for a potential heavy metal binding protein. Nature Genet 3:14–19

    PubMed  Google Scholar 

  7. Danks DM (1989) Disorders of copper transport. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGraw Hill, New York, pp 1411–1431

    Google Scholar 

  8. Danks DM (1990) Menkes' disease In: Fernandes J, Saudubray J-M, Tada K (eds) Inborn metabolic diseases. Springer, Berlin Heidelberg New York, pp 515–521

    Google Scholar 

  9. Danks DM, Campbell PE, Stevens BJ, Mayne V, Cartwright E (1972) Menkes's kinky hair syndrome. Pediatrics 50:188–201

    PubMed  Google Scholar 

  10. De Groot CJ Wijburg FA, Barth PG, Bolhuis PA, Peelen E, Abeling NGG, Hamer CJA van den (1989) Vitamin C treatment in Menkes' Disease: failure to affect biochemical and clinical parameters. J Inherit Metab Dis 12 [Suppl 2]:389–392

    PubMed  Google Scholar 

  11. Garaica AD (1984) The failure of parenteral copper therapy in Menkes kinky hair syndrome. Eur J Pediatr 142:98–102

    PubMed  Google Scholar 

  12. Gerdes AM, Tønnesen T, Pergament E, Sander C, Baerlocher KE, Wartha R, Güttler F, Horn N (1988) Variability in clinical expression of Menkes syndrome. Eur J Pediatr 148:132–135

    PubMed  Google Scholar 

  13. Ghazali S, Barratt TM (1974) Urinary excretion of calcium and magnesium in children. Arch Dis Child 49:97–101

    PubMed  Google Scholar 

  14. Grover WD, Scrutton MC (1975) Copper infusion therapy in trichopoliodystrophy. J Pediatr 86:216–220

    PubMed  Google Scholar 

  15. Grover WD, Johnson WC, Henkin RI (1979) Clinical and biochemical aspects of trichopoliodystrophy. Ann Neurol 5:65–71

    PubMed  Google Scholar 

  16. Grover WD, Henkin RI, Schwarz M, Brodsky N, Hobdell E, Stolk JM (1982) A defect in catecholamine metabolism in kinky-hair disease. Ann Neurol 12:263–266

    PubMed  Google Scholar 

  17. Halbrügge T, Gerhardt T, Ludwig J, Heidbreder E, Graefe K-H (1988) Assay of catecholamines and dihydroxyphenyl-ethylenglycol in human plasma and its application in orthostasis and mental stress. Life Sci 43:19–26

    PubMed  Google Scholar 

  18. Harris ED (1991) Copper transport: an overview. Proc Soc Exp Biol Med 196:130–140

    PubMed  Google Scholar 

  19. Hartter DE, Barnea A (1988) Brain tissue accumulates67copper by two ligand-dependent saturable processes. J Biol Chem 263:799–805

    PubMed  Google Scholar 

  20. Horn N, Tønnesen T, Tümer Z (1992) Menkes disease: an X-linked neurological disorder of the copper metabolism. Brain Pathol 2:351–362

    PubMed  Google Scholar 

  21. Katz BM, Barnea A (1990) The ligand specificity for uptake of complexed copper-67 by brain hypothalamic slices is a function of copper concentration and copper: ligand molar ratio. J Biol Chem 265:2017–2021

    PubMed  Google Scholar 

  22. Kozlowski K, Walker-Smith JA (1973) Bone changes in Menkes' kinky hair syndrome. Radiol Diagn 6:693–700

    Google Scholar 

  23. Loyola MA, Dodson WE (1981) Metabolic consequences of trichopoliodystrophy. J Pediatr 98:588–591

    PubMed  Google Scholar 

  24. Maehara M, Ogasawara N, Mizutani N, Watanabe K, Suzuki S (1983) Cytochrome c oxidase deficiency in Menkes kinky hair disease. Brain Dev 5:533–540

    PubMed  Google Scholar 

  25. Man in't Veld AJ, Boomsma F, Moleman P, Schalekamp MADH (1987) Congenital dopamine-beta-hydroxylase deficiency. Lancet 1:183–188

    PubMed  Google Scholar 

  26. Nadal D, Baerlocher K (1988) Menkes' disease: long-term treatment with copper and d-penicillamine. Eur J Pediatr 147:621–625

    PubMed  Google Scholar 

  27. Nooijen JL, Groot CJ de, Hamer CJA van den, Monnens LAH, Willemse J, Niermeijer MF (1981) Trace element studies in three patients and a fetus with Menkes' disease: effect of copper therapy. Pediatr Res 15:284–289

    PubMed  Google Scholar 

  28. Passon PG, Peuler JD (1973) A simplified radiometric assay for plasma norepinephrine and epinephrine. Anal Biochem 51:618–631

    PubMed  Google Scholar 

  29. Prohaska JR (1987) Functions of trace elements in brain metabolism. Physiol Rev 67:858–901

    PubMed  Google Scholar 

  30. Sherwood G, Sarkar B, Sass-Kortsak A (1989) Copper histidinate therapy in Menkes' disease: prevention of progressive neurodegeneration. J Inherit Metab Dis 12 [Suppl 2]:393–396

    PubMed  Google Scholar 

  31. Tønnesen T, Horn N (1989) Prenatal and postnatal diagnosis of Menke's disease, an inherited disorder of copper metabolism. J Inherit Metab Dis 12 [Supp. 1]:207–214

    PubMed  Google Scholar 

  32. Tümer Z, Tommerup N, Tønnesen T, Kreuder J, Craig IW, Horn N (1992) Mapping of the Menkes locus to Xq13.3 distal to the X-inactivation center by an intrachromosomal insertion of the segment Xq13.3–q21.2. Hum Genet 88:668–672

    PubMed  Google Scholar 

  33. Tümer Z, Chelly J, Tommerup N, Ishikawa-Brush Y, Tønnesen T, Monaco AP, Horn N (1992) Characterization of a 1.0 Mb YAC contig spanning two chromosome breakpoints related to Menkes disease. Hum Mol Genet 7:483–489

    Google Scholar 

  34. Wesenberg RL, Gwinn JL, Barnes GR (1969) Radiological findings in the kinky-hair syndrome. Radiology 92:500–506

    PubMed  Google Scholar 

  35. Wheeler EM, Roberts PF (1976) Menkes' steely hair syndrome. Arch Dis Child 51:269–274

    PubMed  Google Scholar 

  36. Williams DM, Atkin CL, Frens DB, Bray PF (1977) Menkes' kinky hair syndrome: studies of copper metabolism and long term copper therapy. Pediatr Res 11:823–826

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Children's Hospital, Justus Liebig University, Feulgenstrasse 12, D-35385, Giessen, Germany

    J. Kreuder, A. Otten & D. Dralle

  2. Department of Pharmacology, Johannes Gutenburg University, D-55131, Mainz, Germany

    H. Fuder

  3. The John F. Kennedy Institute, DK-2600, Glostrup, Denmark

    Z. Tümer, T. Tønnesen & N. Horn

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  1. J. Kreuder
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  2. A. Otten
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  5. T. Tønnesen
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  6. N. Horn
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  7. D. Dralle
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Kreuder, J., Otten, A., Fuder, H. et al. Clinical and biochemical consequences of copper-histidine therapy in Menkes disease. Eur J Pediatr 152, 828–832 (1993). https://doi.org/10.1007/BF02073380

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  • DOI: https://doi.org/10.1007/BF02073380

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