Skip to main content

Menkes disease: a genetic defect of copper transport

  • Chapter
  • 100 Accesses

Abstract

Menkes disease was first described in 1962 [1] and involved five patients in the same family who all died before the age of three years. They all displayed similar clinical symptoms. Pedigree analysis revealed that the disease was limited to males and was inherited in a sex-linked recessive manner. All patients gained very little weight in the months following birth despite maintaining a normal diet. Hair abnormalities were present in all the affected children. Hair appeared coarse and brittle having an ivory-white colour due to depigmentation. Microscopic analysis revealed that it was either twisted, of varying caliber or fractured at regular intervals. Patients developed seizures between the ages of two and fifteen months. Postmortem examination of patients showed widespread degeneration in the cerebrum and cerebellum, the overall brain size being significantly smaller than average. Over the years since the first report, there has been an increasing number of case reports conforming to the original description of the disease. Subsequently, other clinical features were also reported, including hypothermia, thrombosis, hyperbilirubinaemia, bone changes, arterial rupture and characteristic facies. Menkes disease patients die before the age of three years. In this chapter, we will discuss the biochemical, clinical, genetic and therapeutic aspects of Menkes disease.

Keywords

  • Human Serum Albumin
  • Lysyl Oxidase
  • Copper Transport
  • Menkes Disease
  • Cutis Laxa

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-94-011-3963-2_13
  • Chapter length: 9 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   129.00
Price excludes VAT (USA)
  • ISBN: 978-94-011-3963-2
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   169.99
Price excludes VAT (USA)
Hardcover Book
USD   249.00
Price excludes VAT (USA)

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Menkes JH, Alter M, Steigleder GK, Weakly DR, Sung JH. A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. Pediatrics. 1962;23:764–779.

    Google Scholar 

  2. Danks DM. Of mice and men, metals and mutations. J Med Genet. 1984;23:99–106.

    CrossRef  Google Scholar 

  3. Danks DM, Campbell PE, Walker-Smith J et al. Menkes kinky-hair syndrome. Lancet. 1972;1:1100–1103.

    PubMed  CrossRef  CAS  Google Scholar 

  4. DiDonato M, Sarkar B. Copper transport and its alterations in Menkes and Wilson diseases. Biochem Biophys Acta. 1997;1360:3–16.

    PubMed  CrossRef  CAS  Google Scholar 

  5. Türner Z, Chelly J, Tommerup N et al. Characterization of a 1.0 mb YAC contig spanning two chromosome breakpoints related to Menkes disease. Hum Mol Genet. 1992;1:483–489.

    CrossRef  Google Scholar 

  6. Türner Z, Tommerup N, Tønnesen T, Kreuder J, Craig IW, Horn N. 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. 1992;88:668–672.

    CrossRef  Google Scholar 

  7. Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J. Isolation of candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nature Genet. 1993;3:7–13.

    PubMed  CrossRef  CAS  Google Scholar 

  8. Chelly J, Türner Z, Tønneson T et al. Isolation of a candidate gene for Menkes disease that encodes potential heavy metal binding protein. Nature Genet. 1993;3:14–19.

    PubMed  CrossRef  CAS  Google Scholar 

  9. Mercer JFB, Livingstone J, Hall B et al. Isolation of a partial candidate gene for Menkes disease by positional cloning. Nature Genet. 1993;3:20–25.

    PubMed  CrossRef  CAS  Google Scholar 

  10. Odermatt A, Suter H, Krapf R, Solioz M. An ATPase Operon involved in copper resistance by Enterococcus hirae. Ann NY Acad Sci. 1992;671:484–486.

    PubMed  CrossRef  CAS  Google Scholar 

  11. Odermatt A, Suter H, Krapf R, Solioz M. Primary structure of two P-type ATPases involved in copper homeostasis in Enterococcus hirae. J Biol Chem. 1993;268:12775–12779.

    PubMed  CAS  Google Scholar 

  12. Danks DM. Disorder of copper transport. In: Metabolic basis of inherited disease. Scriver CR, Beandel AI, Sly WS, Valle D, eds. 1995:2211–2235.

    Google Scholar 

  13. Garnica AD. The failure of parenteral copper therapy in Menkes kinky hair syndrome. Eur J Pediatr. 1984;142:98–102.

    PubMed  CrossRef  CAS  Google Scholar 

  14. Sarkar B, Kruck T. Copper amino acid complexes in human serum. New York: Academic Press; 1996:183–196.

    Google Scholar 

  15. Neuman PZ, Sass-Kortsak A. The state of copper in human serum: Evidence for an amino acid-bound fraction. J Clin Invest. 1967;46:646–658.

    CrossRef  Google Scholar 

  16. Lau S, Sarkar B. Ternary co-ordination complex between human serum albumin, copper (II) and L-histidine. J Biol Chem. 1971;246:5938–5943.

    PubMed  CAS  Google Scholar 

  17. Tabata M, Sarkar B. Equilibrium and spectroscopic studies of the ternary system: L-histidine, copper (II), and the native sequence peptide representing the copper (II)-transport site of human serum albumin. Can J Chem. 1985;63:3117–3121.

    CrossRef  CAS  Google Scholar 

  18. Tabata M, Sarkar B. Kinetic mechanism of copper (II)-transfer between the native sequence peptide representing the copper (II)-transport site of human serum albumin and L-histidine. CanJChem. 1985;63:3111–3116.

    CAS  Google Scholar 

  19. Sarkar B, Wigfield Y. Evidence for albumin-Cu(II)-amino acid ternary complex. Can J Biochem. 1968;46:601–607.

    PubMed  CrossRef  CAS  Google Scholar 

  20. Laussac JP, Sarkar B. Characterization of copper (II)-and nickel (II)-transport site of human serum albumin. Studies of copper (II) and nickel (II) binding to peptide 1–24 of human serum albumin by 13C and 1H NMR spectroscopy. Biochemistry. 1984;23:2832–2838.

    PubMed  CrossRef  CAS  Google Scholar 

  21. Sass-Kortsak A, Clarke R, Harris DIM, Neumann PZ, Sarkar B. The biological transport of copper. Progr Neuro-Genet. 1967:625-631.

    Google Scholar 

  22. Harris DIM, Sass-Kortsak A. The influence of amino acids on copper uptake by rat liver slices. J Clin Invest. 1967;46:659–667.

    PubMed  CrossRef  CAS  Google Scholar 

  23. Weiner AL, Cousins RJ. Copper accumulation and metabolism in primary monolayer cultures of rat liver parenchymal cells. Biochim Biophys Acta. 1980;629:113–125.

    PubMed  CrossRef  CAS  Google Scholar 

  24. Darwish HM, Cheney JC, Schmitt RC, Ettinger MJ. Mobilization of copper (II) from plasma components and mechanisms of hepatic copper transport. Am J Physiol. 1984;246:G72–G79.

    PubMed  CAS  Google Scholar 

  25. McArdle HJ, Guthrie JR, Leigh-Ackland M, Danks DM. Albumin has no role in the uptake of copper by human fibroblasts. J Inorg Biochem. 1987;31:123–131.

    PubMed  CrossRef  CAS  Google Scholar 

  26. McArdle HJ, Gross SM, Danks DM. The uptake of copper by mouse hepatocytes. J Cell Physiol. 1988;136:373–378.

    PubMed  CrossRef  CAS  Google Scholar 

  27. Mas A, Sarkar B. Uptake of 67Cu by isolated human trophoblast cells. Biochim Biophys Acta. 1992;1135:123–128.

    PubMed  CrossRef  CAS  Google Scholar 

  28. Sarkar B. Recent trends in the application of coordination chemistry in biology and medicine. Oxford and New York: Pergamon Press; 1980:191–200.

    Google Scholar 

  29. Kruck T, Sarkar B. Equilibria of the simultaneously existing multiple species in the copper (II)-L-histidine system. Can J Chem. 1973;51:3549–3554.

    CrossRef  Google Scholar 

  30. Kruck T, Sarkar B. Structure of the species in the copper (II)-L-histidine system. Can J Chem. 1973;51:3563–3571.

    CrossRef  CAS  Google Scholar 

  31. Sarkar B. Specificity of metal-binding in normal physiology and biochemical alterations in disease conditions: Wilson’s and Menkes diseases. In: Arora RB, Vohora SB, Khan MSY, eds. The Proceedings of the First International Conference on Elements in Health and Disease. New Delhi: Institute of History of Medicine and Medical Research; 1984:27–41.

    Google Scholar 

  32. Sherwood G, Sarkar B, Sass-Kortsak A. Copper histidine therapy in Menkes disease: prevention of progressive neurodegeneration. J Inher Metab Dis. 1989;2:393–396.

    CrossRef  Google Scholar 

  33. Sarkar B, Lingertat-Walsh K, Clarke JTR. Copper-histidine therapy for Menkes disease. J Pediatr. 1993;123:828–830.

    PubMed  CrossRef  CAS  Google Scholar 

  34. Briggs J, Finch P, Matulewicz MC et al. Complexes of copper (II), calcium, and the metal ions with carbohydrates: Thin-layer ligand-exchange chromatography and determination of relative stabilities of complexes. Carbohydr Res. 1981;97:181–188.

    CrossRef  CAS  Google Scholar 

  35. Kreuder J, Otten A, Fuder H et al. Clinical and biochemical consequences of copper-histidine therapy in Menkes disease. Eur J Pediatr. 1993;152:828–832.

    PubMed  CrossRef  CAS  Google Scholar 

  36. Türner Z, Horn N, Tønnesen T, Christodolou J, Clarke JTR, Sarkar B. Efficacy of early copper-histidine treatment for Menkes disease. Nature Genet. 1996;12:11–13.

    CrossRef  Google Scholar 

  37. Hamer DH. ‘Kinky hair’ disease sheds light on copper metabolism. Nature Genet. 1993;3:3–4.

    PubMed  CrossRef  CAS  Google Scholar 

  38. Sarkar B. Transport form of copper in human serum. In: Sarkar B, ed. Biological Aspects of Metals and Metal-Related Diseases. New York: Raven Press; 1983:23–40.

    Google Scholar 

  39. Hartler DE, Barnea A. Brain tissue accumulates 67copper by two ligand-dependent saturable processes. J Biol Chem. 1988;263:799–805.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 1998 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Sarkar, B. (1998). Menkes disease: a genetic defect of copper transport. In: Rainsford, K.D., Milanino, R., Sorenson, J.R.J., Velo, G.P. (eds) Copper and Zinc in Inflammatory and Degenerative Diseases. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3963-2_13

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-3963-2_13

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-5757-8

  • Online ISBN: 978-94-011-3963-2

  • eBook Packages: Springer Book Archive