Skip to main content

Advertisement

SpringerLink
Log in

Idiopathic copper toxicosis: is abnormal copper metabolism a primary cause of this disease?

  • Case Report
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

Abstract

Idiopathic copper toxicosis (ICT) is characterized by marked copper deposition, Mallory-Denk body (MDB) formation and severe hepatic injury. Although the characteristics are apparently different from Wilson disease, large amounts of copper accumulate in the liver of the patients. We extensively treated a patient with ICT to reduce the body copper, however, the patient needed liver transplantation. Previous liver biopsy revealed high copper content. But extirpated liver contained an extremely small amount of copper, although MDBs and severe inflammation remained. These phenomena suggest abnormal copper metabolism is not the principle cause of ICT but some other abnormality must exist.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Scheinberg IH, Sternlieb I (1996) Wilson disease and idiopathic copper toxicosis. Am J Clin Nutr 63:842S–845S

    Article  CAS  Google Scholar 

  2. Müller T, Müller W, Feichtinger H (1998) Idiopathic copper toxicosis. Am J Clin Nutr 67:1082S–1086S

    Article  Google Scholar 

  3. Nayak NC, Chitale AR (2013) Indian childhood cirrhosis (ICC) and ICC-like diseases: the changing scenario of facts versus notions. Indian J Med Res 137:1029–1042

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Tatsumi Y, Kato A, Kato K, Hayashi H (2018) The interactions between iron and copper in genetic iron overload syndromes and primary copper toxicoses in Japan. Hepatol Res 48:679–691

    Article  CAS  Google Scholar 

  5. Müller T, Langner C, Fuchsbichler A, Heinz-Erian P, Ellemunter H, Schlenck B, Bavdekar AR, Pradhan AM, Pandit A, Müller-Höcker J, Melter M, Kobayashi K, Nagasaka H, Kikuta H, Müller W, Tanner MS, Sternlieb I, Zatloukal K, Denk H (2004) Immunohistochemical analysis of Mallory bodies in Wilsonian and non-Wilsonian hepatic copper toxicosis. Hepatology 39:963–969

    Article  Google Scholar 

  6. Zatloukal K, French SW, Stumptner C, Strnad P, Harada M, Toivola DM, Cadrin M, Omary MB (2007) From Mallory to Mallory-Denk bodies: what, how and why? Exp Cell Res 313:2033–2049

    Article  CAS  Google Scholar 

  7. Tanner MS, Bhave SA, Pradhan AM, Pandit AN (1987) Clinical trials of penicillamine in Indian childhood cirrhosis. Arch Dis Child 62:1118–1124

    Article  CAS  Google Scholar 

  8. Müller T, Schäfer H, Rodeck B, Haupt G, Koch H, Bosse H, Welling P, Lange H, Krech R, Feist D, Mühlendahl KE, Brämswig J, Feichtinger H, Müller W (1999) Familial clustering of infantile cirrhosis in Northern Germany: a clue to the etiology of idiopathic copper toxicosis. J Pediatr 135:189–196

    Article  Google Scholar 

  9. Tanner MS (1998) Role of copper in Indian childhood cirrhosis. Am J Clin Nutr 67(5 Suppl):1074S–S1081

    Article  CAS  Google Scholar 

  10. Patra S, Vij M, Kancherala R, Samal SC (2013) Is Indian childhood cirrhosis an extinct disease now? Indian J Pediatr 80:651–654

    Article  Google Scholar 

  11. Nayak NC, Marwaha N, Kalra V, Roy S, Ghai OP (1981) The liver in siblings of patients with Indian childhood cirrhosis: a light and electron microscopic study. Gut 22:295–300

    Article  CAS  Google Scholar 

  12. Roberts EA, Schilsky ML (2008) Diagnosis and treatment of Wilson disease: an update. Hepatology 47:2089–2111

    Article  CAS  Google Scholar 

  13. European Association for the Study of the Liver (2012) EASL clinical practice guidelines: Wilson’s disease. J Hepatol 56:671–685

    Article  Google Scholar 

  14. Harada M (2014) Pathogenesis and management of Wilson disease. Hepatol Res 44:395–402

    Article  Google Scholar 

  15. Hayashi H, Shinohara T, Goto K, Fujita Y, Murakami Y, Hattori A, Tatsumi Y, Shimizu A, Ichiki T (2012) Liver structures of a patient with idiopathic copper toxicosis. Med Mol Morphol 45:105–109

    Article  Google Scholar 

  16. Thattil R, Dufour JF (2013) Hepatocellular carcinoma in a non-cirrhotic patient with Wilson’s disease. World J Gastroenterol 19:2110–2113

    Article  Google Scholar 

  17. Oe S, Miyagawa K, Honma Y, Harada M (2016) Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease. Exp Cell Res 347:192–200

    Article  CAS  Google Scholar 

  18. Scheinberg IH, Sternlieb I (1994) Is non-Indian childhood cirrhosis caused by excess dietary copper? Lancet 344:1002–1004

    Article  CAS  Google Scholar 

  19. Nagasaka H, Kobayashi K, Yorifuji T, Kage M, Kimiura A, Takayanagi M, Kikuta H, Egawa H, Tanaka K, Inui A, Fujisawa T, Ohtake A (1999) Indian childhood cirrhosis-like disease in a Japanese boy undergoing liver transplantation. J Pediatr Gastroenterol Nutr 29:598–600

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by JSPS KAKENHI Grant No. 18K07988 to MH.

Author information

Authors and Affiliations

  1. Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan

    Masaru Harada, Yuichi Honma, Keiichiro Kumamoto, Shinji Oe, Aya Tanimoto, Tsukasa Karasuyama, Akitoshi Yoneda & Michihiko Shibata

  2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Tomoharu Yoshizumi & Noboru Harada

  3. Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Keiichiro Kumamoto

  4. Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Kei Yabuki

Authors
  1. Masaru Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuichi Honma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomoharu Yoshizumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Keiichiro Kumamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shinji Oe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Noboru Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aya Tanimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kei Yabuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tsukasa Karasuyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Akitoshi Yoneda
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Michihiko Shibata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masaru Harada.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harada, M., Honma, Y., Yoshizumi, T. et al. Idiopathic copper toxicosis: is abnormal copper metabolism a primary cause of this disease?. Med Mol Morphol 53, 50–55 (2020). https://doi.org/10.1007/s00795-019-00227-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-019-00227-4

Keywords

Search

Navigation