Long-term evaluation of urinary copper excretion and non-caeruloplasmin associated copper in Wilson disease patients under medical treatment

  • Jan Pfeiffenberger
  • Christine Marie Lohse
  • Daniel Gotthardt
  • Christian Rupp
  • Markus Weiler
  • Ulrike Teufel
  • Karl Heinz Weiss
  • Annika GaussEmail author
Original Article



Urinary copper excretion rates and non-caeruloplasmin associated copper concentrations are increased in patients with Wilson disease. However, there is little literature describing the monitoring of these parameters over the long term.


This is a monocentric retrospective study including data collected between 2003 and 2015 from 321 patients with Wilson disease by chart review. The patients were under therapy with D-penicillamine, trientine, or zinc. 24-h urinary copper excretion rates, non-caeruloplasmin associated copper, and total serum copper concentrations were determined at the start of therapy, as well as 6, 12, 18, 24, 36, and ≥ 60 months after the start of therapy. For patients taking chelating agents, all parameters were measured while under continued therapy, as well as after a 48-h dose interruption. A mathematical formula to predict 24-h urinary copper excretion rates under different therapies was established.


In all treatment groups, urinary copper excretion rates decreased over time, but the inter-individual variation of the results was high. Non-caeruloplasmin associated copper concentrations tended to decline over time, but with a higher variation of results than that observed for urinary copper excretion rates.


Due to their variability, urinary copper excretion rates and serum copper concentrations are less than ideal parameters by which to monitor the benefit of a copper-reducing therapy. Urinary copper excretion rates seem to be more suitable than non-caeruloplasmin associated copper concentrations for this purpose.


Chelator Non-caeruloplasmin associated serum copper Long term Urinary copper excretion Wilson disease Zinc 



We are grateful to the patients participating in this trial. We thank Mrs. Jessica Langel for the documentary assistance.


This is a non-funded study.

Compliance with ethical standards

Conflict of interest

None of the authors has any competing interests to declare.


  1. Bandmann O, Weiss KH, Kaler SG (2015) Wilson's disease and other neurological copper disorders. Lancet Neurol 14:103-113Google Scholar
  2. Brewer GJ (1995) Practical recommendations and new therapies for Wilson’s disease. Drugs 50:240–249CrossRefPubMedGoogle Scholar
  3. Das SK, Ray K (2006) Wilson’s disease: an update. Nat Clin Pract Neurol 2:482–493CrossRefPubMedGoogle Scholar
  4. European Association for Study of Liver (2012) EASL clinical practice guidelines: Wilson’s disease. J Hepatol 56:671–685CrossRefGoogle Scholar
  5. Ferenci P, Caca K, Loudianos G et al (2003) Diagnosis and phenotypic classification of Wilson disease. Liver Int 23:139–142CrossRefPubMedGoogle Scholar
  6. Gaffney D, Fell GS, O’Reilly DS (2000) ACP best practice no 163. Wilson’s disease: acute and presymptomatic laboratory diagnosis and monitoring. J Clin Pathol 53:807–812CrossRefPubMedPubMedCentralGoogle Scholar
  7. Martins da Costa C, Baldwin D, Portmann B, Lolin Y, Mowat AP, Mieli-Vergani G (1992) Value of urinary copper excretion after penicillamine challenge in the diagnosis of Wilson’s disease. Hepatology 15:609–615CrossRefPubMedGoogle Scholar
  8. Medici V, Rossaro L, Sturniolo GC (2007) Wilson disease—a practical approach to diagnosis, treatment and follow-up. Dig Liver Dis 39:601–609CrossRefPubMedGoogle Scholar
  9. Müller T, Koppikar S, Taylor RM et al (2007) Re-evaluation of the penicillamine challenge test in the diagnosis of Wilson’s disease in children. J Hepatol 47:270–276CrossRefPubMedGoogle Scholar
  10. Park RH, McCabe P, Fell GS, Russell RI (1991) Wilson’s disease in Scotland. Gut 32:1541–1545CrossRefPubMedPubMedCentralGoogle Scholar
  11. Pfeiffer RF (2007) Wilson’s disease. Semin Neurol 27:123–132CrossRefPubMedGoogle Scholar
  12. Ritland S, Steinnes E, Skrede S (1977) Hepatic copper content, urinary copper excretion, and serum ceruloplasmin in liver disease. Scand J Gastroenterol 12:81–88PubMedGoogle Scholar
  13. Roberts EA, Schilsky ML; American Association for Study of Liver Diseases (AASLD) (2008) Diagnosis and treatment of Wilson disease: an update. Hepatology 47:2089–2111CrossRefPubMedGoogle Scholar
  14. Schilsky ML (2017) Wilson disease: Diagnosis, Treatment, and Follow-up. Clin Liver Dis 21:755-767Google Scholar
  15. Walshe JM (1956) Wilson’s disease; new oral therapy. Lancet 270:25–26CrossRefPubMedGoogle Scholar
  16. Walshe JM (2011) The pattern of urinary copper excretion and its response to treatment in patients with Wilson’s disease. QJM 104:775–778CrossRefPubMedGoogle Scholar
  17. Walshe JM (2012) Serum ‘free’ copper in Wilson disease. QJM 105:419–423CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM 2018

Authors and Affiliations

  1. 1.Department of Gastroenterology and HepatologyUniversity Hospital HeidelbergHeidelbergGermany
  2. 2.Department of NeurologyUniversity Hospital HeidelbergHeidelbergGermany
  3. 3.Department of Pediatrics and Adolescent Medicine, University Medical Center, Medical FacultyUniversity of FreiburgFreiburgGermany

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