Wilson disease is an autosomal recessive disorder of copper transport characterized by reduced copper incorporation into ceruloplasmin, and by impaired copper biliary excretion. This results in progressive copper accumulation in the liver and subsequently in the brain, cornea, and other tissues. So tissue damage and symptoms in WD are the result of the toxic effect of copper overload.
While the incidence of WD is approximately 1/50-100000 live births world wide, in Sardinia it is approximately 1/10000 live births which is one of the highest worldwide
In the last years we have molecularly analyzed 463 WD families from different parts of the Mediterranean. We observed that there is a considerable ethnic variability. There are some mutations that are largely prevalent in the populations analyzed that permits an efficient mutations screening in these populations.
In the Sardinian population we have analyzed 96 WD families and found that the 6 most common mutations account for the molecular defect of 85% of cases. Of them, a single mutation accounts for 60% of total that suggests a founder effect for WD in this population.
A limited screening for the most common mutation in 5290 random DNA samples from subjects of Sardinian descent, detected 122 heterozygotes indicating a carrier rate of 1:43.
Based on these data and according to Hardy-Weinberg we estimated the expected new cases, that are approximately 5 per 15000 newborns per year in this population.
So these data strongly suggest that not only can mutation detection in single cases be used for WD prevention in this population, but probably be used also as a mass screening.
In order to demonstrate or exclude this hypothesis we are planning to set up a three year pilot program of neonatal screening for WD. All newborns in this period will be the target population. We will search in them the 6 most common mutations in this poulationThe results of this pilot program will provide more information on the incidence of WD in our population and on the feasibility, reproducibility, and cost-effectiveness of this approach as a prevention program in this population.