Genetic and clinical characteristics of hereditary transthyretin amyloidosis in endemic and non-endemic areas: experience from a single-referral center in Japan

Hereditary transthyretin (ATTR) amyloidosis is a life-threatening, autosomal dominant, systemic amyloidosis caused by mutant transthyretin. In addition to ATTRV30M in endemic and non-endemic areas, more than 140 non-V30M mutations occur worldwide. The aim of this study was to analyze the clinical characteristics and genetic frequencies of hereditary ATTR amyloidosis. Diagnostic results and clinical manifestations of hereditary ATTR amyloidosis from April 1, 2012, to March 31, 2017, at Amyloidosis Medical Practice Center, Kumamoto University Hospital were analyzed. One hundred and four patients received a diagnosis of symptomatic hereditary ATTR amyloidosis. The following mutations of the TTR gene and their percentages were found: V30M in endemic areas, 10.6%; V30M in non-endemic areas, 51.0%; and non-V30M, 38.5%. The ages at onset of patients with ATTRV30M amyloidosis in non-endemic areas (66.6 ± 8.7 years) and those with non-V30M ATTR amyloidosis (55.8 ± 13.6 years) were significantly higher than those with ATTRV30M amyloidosis in endemic areas (37.0 ± 12.6 years). Of patients with ATTRV30M amyloidosis in endemic and non-endemic areas, and non-V30M ATTR amyloidosis, 63.6, 66.0, and 27.5% initially presented with polyneuropathy, respectively. Of patients with ATTRV30M amyloidosis in endemic areas, 81.8% had a family history of this disease. However, a significantly smaller percentage of patients with ATTRV30M amyloidosis (30.0%) in non-endemic areas and non-V30M ATTR amyloidosis (34.0%) had a family history. Patients with ATTRV30M amyloidosis in non-endemic areas and patients with non-V30M ATTR amyloidosis occurred more frequently than previously believed, and their clinical manifestations were diverse.