Investigative algorithms for disorders affecting plasma copper concentration: a narrative review

Background and Objective: Copper (Cu) disturbances within humans have been associated with a wide range of disease states due to dysregulation of its essential physiological functions. The following article aims to aid the reader in diagnosing the cause of plasma Cu derangements in humans and discusses some of ways in which the biochemistry tests are performed and their limitations. By the end of the article, the reader will be able to order and interpret appropriate investigations when faced with a patient with low or high Cu concentration in plasma. Methods: A focused narrative literature review was performed using PubMed, OMIM and Google. Searches were conducted from September 2024 to September 2025 to identify relevant publications from database inception to September 2025. Key Content and Findings: Within this review are discussed key causes of low Cu, such as Menkes and zinc overload, and causes of high Cu plasma concentrations, such as dietary excess and cholestasis. From this, diagnostic flow charts have been created by the authors, providing a systematic approach for investigations. Conclusions: This article will help healthcare professionals with a practical framework to aid investigation into the cause of Cu concentration abnormalities in human plasma, where the cause is not immediately apparent. These algorithms have been presented and created within the limitations of the laboratory tests discussed within the paper, selected to be widely available.