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

J Inherit Metab Dis. 2019 Mar;42(2):371-380. doi: 10.1002/jimd.12046. Epub 2019 Feb 11.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Chelator; Long term; Non-caeruloplasmin associated serum copper; Urinary copper excretion; Wilson disease; Zinc.

MeSH terms

  • Adolescent
  • Adult
  • Ceruloplasmin / metabolism
  • Chelating Agents / therapeutic use
  • Child
  • Child, Preschool
  • Copper / blood
  • Copper / metabolism
  • Copper / urine*
  • Female
  • Germany
  • Hepatolenticular Degeneration / blood
  • Hepatolenticular Degeneration / drug therapy*
  • Hepatolenticular Degeneration / urine
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Penicillamine / therapeutic use*
  • Regression Analysis
  • Retrospective Studies
  • Trientine / therapeutic use*
  • Young Adult
  • Zinc / therapeutic use*

Substances

  • Chelating Agents
  • Copper
  • Ceruloplasmin
  • Penicillamine
  • Zinc
  • Trientine