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The Mild Form of Menkes Disease: A 34 Year Progress Report on the Original Case

  • M. C. TchanEmail author
  • B. Wilcken
  • J. Christodoulou
Case Report
Part of the JIMD Reports book series (JIMD, volume 9)

Abstract

Classical Menkes disease is a neurodegenerative disorder caused by mutations in the copper-transporting ATPase ATP7A gene which, when untreated, is usually fatal in early childhood. A mild form of Menkes disease was originally reported in 1981 and clinical progress of the patient at 10 years described subsequently. The causative mutation is c.4085C>T in exon 21, causing an alanine to valine substitution in the highly conserved TM7 domain at the C-terminal end of the Menkes protein. Here we report his status at 34 years of age. Intellectual impairment is mild. Ataxia has nearly resolved but motor retardation, dysarthria and an extreme slow speech rate remain. In contrast to patients with the occipital horn syndrome, there have been no connective tissue complications of his mild Menkes disease. He has been under long-term copper therapy for more than 30 years and he continues to enjoy a good quality of life.

References

  1. Alvarez de Santos M, Moreno P (1984) Mild form of Menkes syndrome. Rev Invest Clin 36(2):151–154PubMedGoogle Scholar
  2. Ambrosini L, Mercer JF (1999) Defective copper-induced trafficking and localization of the Menkes protein in patients with mild and copper-treated classical Menkes disease. Hum Mol Genet 8(8):1547–1555CrossRefPubMedGoogle Scholar
  3. Christodoulou J et al (1998) Early treatment of Menkes disease with parenteral copper-histidine: long-term follow-up of four treated patients. Am J Med Genet 76(2):154–164CrossRefPubMedGoogle Scholar
  4. Danks DM (1988) The mild form of Menkes disease: progress report on the original case. Am J Med Genet 30(3):859–864CrossRefPubMedGoogle Scholar
  5. Gerdes AM et al (1988) Variability in clinical expression of Menkes syndrome. Eur J Pediatr 148(2):132–135CrossRefPubMedGoogle Scholar
  6. Inagaki M et al (1988) Atypical form of Menkes kinky hair disease with mitochondrial NADH-CoQ reductase deficiency. Neuropediatrics 19(1):52–55CrossRefPubMedGoogle Scholar
  7. Kaler SG et al (1994) Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus. Nat Genet 8(2):195–202CrossRefPubMedGoogle Scholar
  8. Kaler SG et al (2008) Neonatal diagnosis and treatment of Menkes disease. N Engl J Med 358(6):605–614CrossRefPubMedPubMedCentralGoogle Scholar
  9. Kennerson ML et al (2010) Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy. Am J Hum Genet 86(3):343–352CrossRefPubMedPubMedCentralGoogle Scholar
  10. Lenartowicz M et al (2010) Effects of copper supplementation on the structure and content of elements in kidneys of mosaic mutant mice. Biol Trace Elem Res 136(2):204–220CrossRefPubMedGoogle Scholar
  11. Procopis P, Camakaris J, Danks DM (1981) A mild form of Menkes steely hair syndrome. J Pediatr 98(1):97–99CrossRefPubMedGoogle Scholar
  12. Proud VK et al (1996) Distinctive Menkes disease variant with occipital horns: delineation of natural history and clinical phenotype. Am J Med Genet 65(1):44–51CrossRefPubMedGoogle Scholar
  13. Tsukahara M et al (1994) Occipital horn syndrome: report of a patient and review of the literature. Clin Genet 45(1):32–35CrossRefPubMedGoogle Scholar
  14. Tumer Z et al (1997) Identification of point mutations in 41 unrelated patients affected with Menkes disease. Am J Hum Genet 60(1):63–71PubMedPubMedCentralGoogle Scholar
  15. Westman JA et al (1988) Atypical Menkes steely hair disease. Am J Med Genet 30(3):853–858CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • M. C. Tchan
    • 1
    • 2
    • 5
    Email author
  • B. Wilcken
    • 3
    • 4
  • J. Christodoulou
    • 3
    • 4
  1. 1.Department of Genetic MedicineWestmead HospitalSydneyAustralia
  2. 2.Discipline of Genetic Medicine, Sydney Medical SchoolUniversity of SydneySydneyAustralia
  3. 3.Western Sydney Genetics ProgramThe Children’s Hospital at WestmeadSydneyAustralia
  4. 4.Disciplines of Paediatrics and Child Health and Genetic Medicine, Sydney Medical SchoolUniversity of SydneySydneyAustralia
  5. 5.Department of Genetic MedicineWestmead HospitalWentworthvilleAustralia

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