The role of calculated non-caeruloplasmin-bound copper in Wilson's disease

Abstract

Background US and European guidelines suggest the use of calculated non-caeruloplasmin-bound copper (free copper index) for the diagnosis and management of Wilson's Disease. However, there is concern that the required analytical measurements of caeruloplasmin and copper may not be sufficiently robust at the concentrations usually found. Methods Aliquots of six plasma specimens were sent to laboratories participating in the UK National External Quality Assessment Scheme for copper and caeruloplasmin. The variability of these two reported measurements and the calculated non-caeruloplasmin-bound copper concentrations were compared. The variability of caeruloplasmin reference ranges quoted by laboratories was also investigated. Results No laboratories use the required enzymatic methods in the calculation of non-caeruloplasmin-bound copper. The interlaboratory variations in caeruloplasmin concentrations and calculated non-caeruloplasmin-bound copper concentrations were very considerable so making clinical interpretation unreliable. Wide differences in the caeruloplasmin reference ranges used were also found. Conclusions Such variations of the calculated non-caeruloplasmin-bound copper concentrations and the predominant use of immunological methods for measuring caeruloplasmin preclude a clinical role for this calculated value in the investigation of Wilson's disease.

Keywords: Inborn errors of metabolism; clinical studies.