Is familial amyloid polyneuropathy rare?

Abstract

Familial amyloid polyneuropathy (FAP) is one type of hereditary generalized amyloidosis, initially showing polyneuropathy and autonomic dysfunction but with later involvement of many visceral organs. The disease is caused by a mutation in the transthyretin (TTR) gene, which produces an amyloidogenic variant form of TTR (ATTR), thus leading to the designation ATTR type FAP.1 Up to now, more than 100 mutations have been identified as a cause of the gene abnormality in this disease,2 but the substitution of methionine for valine at position 30 (ATTRVal30Met) is the most common one that causes the classic phenotype of FAP. With regard to the clinical concept of ATTR type FAP, the following features have been emphasized.3 The disease occurs mainly in four endemic areas (the Oporto area in Portugal, Skelleftea in Sweden, and Arao and Ogawa in Japan) where it is inherited as an autosomal dominant trait with equal sex distribution. The age at onset is the late 20s to early 40s and polyneuropathy is consistently associated with sensory dissociation; that is, pain and thermal sensations are predominantly affected at an early stage of the disease. Various autonomic dysfunctions, including severe …