Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Hereditary transthyretin amyloidosis is caused by pathogenic variants in the TTR gene and typically manifests, alongside cardiac and other organ dysfunctions, with a rapidly progressive sensorimotor and autonomic polyneuropathy (ATTRv-PN) leading to severe disability. While most prospective studies have focussed on endemic ATTRv-PN, real-world data on non-endemic, mostly late-onset ATTRv-PN are limited. ⋯ In non-endemic, mostly late-onset ATTRv-PN, cardiac involvement assessed by NT-proBNP is a strong prognosticator for overall survival. Long-term treatment with tafamidis is safe and efficacious. Neurologic disease severity at the start of treatment is the main predictor for ATTRv-PN progression on tafamidis.
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Hereditary transthyretin (ATTRv) amyloidosis is of autosomal dominant transmission, caused by a spectrum of mutations in the transthyretin (TTR) gene. The ATTRV30M (p.Val50Met) is the most frequent substitution in Europe. Northern Sweden is a known cluster for ATTRV30M amyloidosis patients due to high prevalence of the mutation rate, with homozygous cases. First symptoms occur generally during the 6th decade. Previous studies reported low penetrance in this area and possible anticipation in families. In order to refine our knowledge of the genetic aspects, penetrance and factors that influence the disease's risk, we performed a comprehensive study of ATTRV30M families in Sweden. ⋯ Our study provides new data on the genetics of ATTRV30M families in Sweden, including the occurrence of anticipation and on penetrance. Both are increased in case of maternal inheritance and in male patients. Overall, gender seems to be a factor that substantially modulates the AO of the disease, in this area. Clinically, these findings are of importance to guide the management of sibships and the monitoring of mutation carriers.