Genetic epidemiology of familial amyloid polyneuropathy in the Balearic Islands (Spain)

Abstract

Between 1976 and 2003, we diagnosed 144 patients with familial amyloid polyneuropathy (FAP) in the Balearic Islands (Spain). Analysis of genetic epidemiological data from 102 confirmed patients showed 62% were men. Parental transmission was paternal in 38, maternal in 25, and unknown in 39. No family history of FAP was found in 32 patients. TTRVal30Met associated with haplotype I was present in the individuals studied. Mean age-at-onset was 45.7 years which lies between that of Sweden and those of Portugal, Japan and Brazil. Duration of FAP was of 9.7 years. Age-at-onset, age-at-death, duration and fertility were similar between sexes. Twenty-nine intergeneration familial pairs of patients were ascertained. Raw anticipation was positive in twenty-four pairs, zero in one, and negative in four. Differences greater than 9 years between age-at-onset of the first and second member were considered relevant; positive relevant anticipation was found in 76% of the whole pairs. The frequency of positive anticipation of parent-child pairs was not significantly different than those described in the Swedish and Portuguese series. Significant positive correlation in age-at-onset was confirmed in twenty-seven types of pairs supporting the hypothesis that a genetic factor may modulate age-at-onset. The Balearic focus of FAP is expanding and constitutes a public health problem.

• Hereditary amyloidosis
• familial amyloid polyneuropathy
• TTRVal30Met mutation
• haplotype I
• anticipation of age-at-onset

FAP, familial amyloid polyneuropathy; TTR, transthyretin

FAP, familial amyloid polyneuropathy; TTR, transthyretin