Epidemiologic study of hepatolenticular degeneration (Wilson's disease) in Sardinia (1902-1983)

Abstract

From 1902From to 1983 cases of hepatolenticular degeneration (HLD) were discovered in Sardinia, with a mean frequency, in reference to number of live births, of 27.7 and a sex ratio of 1.83. The prevalence of the disease was seen to be higher over the last few decades. With regard to the geographic distribution of the disease, 3 high-frequency areas were evident, in Barbagia, in Campidano, and in the area surrounding the city of Sassari. In 38.23% of cases, the clinical picture was of hepatoneurologic type; hepatic forms have become more frequent over the last decades. The first symptoms were observed at mean age of 15 years 8 months. The number of asymptomatic cases was fairly consistent (22.05%). The median survival rate in subjects who received inadequate therapy was 6 years 4 months. Only 3 patients of the 45 treated with adequate therapy died. The gene frequency, calculated by the application of Dahlberg's formula, was extremely high.

The homozygosity index (HI) approach reveals high allele frequency for Wilson disease in the Sardinian population

“…13,14 The most remote areas of the island (namely mountains and internal hills) where genetic isolation is stronger coincide with a higher local prevalence of recessive disorders like WD. 9 Furthermore, the presence of a small number of individuals born to consanguineous parents was taken into account in the computation of F (for further details, see online Supplementary Information).…”

“…8 In contrast to mainland Europe, the Sardinian population shows a WD prevalence that has been estimated to be 1/10 000-1/7000, one of the highest worldwide. 6,9 All these estimates have been inferred through classical approaches, such as the frequencies of clinically diagnosed cases, or from the findings of autopsy series, 8 and as such they are likely to suffer from an underdiagnosis bias. In support of this hypothesis, a recent molecular neonatal screening in the Sardinian population reported a WD gene frequency of 1.92% and a resulting prevalence of 1/2707 live births.…”

Neurologic Wilson’s Disease and its Management - An Update

“…Then, between early childhood and the fifth or sixth decade of life, but with a peak incidence of around 17 years, the patient presents with hepatic, neurologic, and psychiatric manifestations. 19 Those with a primarily hepatic presentation appear to have an earlier age at presentation than those with the primarily neurologic presentation. [19][20] Although Wilson's disease usually presents in childhood to early adulthood, a wider range of age at onset is recognized.…”

“…19 Those with a primarily hepatic presentation appear to have an earlier age at presentation than those with the primarily neurologic presentation. [19][20] Although Wilson's disease usually presents in childhood to early adulthood, a wider range of age at onset is recognized. This review deals primarily with neurologic Wilson's disease,and hepatic manifestations will be briefly considered .…”

“…The result is a rapid removal of tissue copper, which is then bound in the serum by TM, reducing potential copper toxicity, and significantly less neurologic worsening compared to penicillamine or trientine. [17][18][19][20] TM has a good safety profile. 48,53 There is a 10-15% incidence of over treatment, anemia/leukopenia, responsive to lowering the dose.…”