Wilson’s disease (WD) is an autosomal recessive genetic condition which leads to the accumulation of copper in the body, causing life-threatening hepatic and neurological damage. Copper is an essential mineral that supports several bodily functions, the gene ATP7B controls its removal from the body, from hepatocytes into bile. Mutations in the ATP7B gene lead to the development of WD.
Currently serum ceruloplasmin levels are used to screen for Wilson’s disease. Ceruloplasmin is a protein that carries copper round the body. It has a poor sensitivity and specificity for diagnosing Wilson’s disease. Other tests including 24-hour urine collection and genetic testing are costly and time-consuming, leaving ceruloplasmin as the first-line investigation.
There is growing research that there is a mismatch between genetic and clinical prevalence of Wilson’s disease. Given this, there is a question as to whether milder or partial ATP7B disruption may contribute to other, common, liver conditions including Steatotic Liver Disease (SLD), or whether WD is being misdiagnosed as SLD. SLD has overlapping biochemical features with WD including hepatic transaminitis and liver steatosis on non-invasive imaging. It is a growing epidemic and affects more than 1/3rd of the general population. Over the last decade there has been an increase in diagnostic programmes for SLD and as part of the diagnostic work-up, screening for WD with ceruloplasmin levels will increase. In this new landscape of liver disease, it’s unclear what the impact on WD diagnoses will be.
Over the next 6-12 months this project will use the UK Biobank’s large-scale datasets to determine the relationship between ATP7B mutation, WD and SLD.