Endemic Tyrolean infantile cirrhosis: an ecogenetic disorder

Abstract

Background: 138 infants and young children died from an endemic infantile liver cirrhosis in a circumscribed rural area of western Austria between 1900 and 1974. Frequency of the disease peaked between 1930 and 1960. It has disappeared from this area since 1974.

Methods: Clinical and genetic data on the patients was gathered; pedigrees analysed and ethnographic studies and interviews were undertaken.

Findings: The disease, which was clinically and pathologically indistinguishable from Indian childhood cirrhosis and hepatic copper toxicosis, was transmitted by autosomal recessive inheritance. Cow's milk, contaminated with copper from untinned copper or brass vessels, may have contributed to the development of copper toxicosis. Replacement of untinned copper cooking utensils by modern industrial vessels has eradicated the disease.

Interpretation: Our findings strongly suggest that the endemic Tyrolean childhood cirrhosis-and by analogy non-Wilsonian hepatic copper toxicosis occurring elsewhere-is an ecogenetic disorder requiring the involvement of both genetic and environmental factors for the disease to become manifest.