Hereditary transthyretin amyloidosis (ATTRv) is a fatal autosomal dominant disorder caused by pathogenic variants in the TTR gene. Various variants cause destabilization of transthyretin tetramers and extracellular deposition of misfolded amyloid fibrils in different tissues, resulting in highly variable phenotypes. The peripheral nervous system is the most frequently involved organ, followed by the heart, the eyes, the kidneys, and the gastrointestinal tract. In contrast to the most common p. Val50Met variant in Western countries, the p. Ala117Ser variant constitutes the majority of ATTRv cases in Taiwan. Increased awareness, noninvasive imaging, and genetic testing have improved early identification; however, diagnostic delay remains a significant challenge because of phenotypic heterogeneity and variable penetrance. Recent therapeutic developments-such as transthyretin stabilizers, small interfering RNAs and antisense oligonucleotide-based gene silencing, and investigational gene-editing approaches-have transformed prognosis. This review summarizes the updated evidence concerning the epidemiology, pathophysiology, clinical presentation, and diagnostic strategies, with an emphasis on evolving treatments. Special attention is given to early detection, the integration of multidisciplinary care, and the management of asymptomatic carriers, highlighting the importance of continued research to optimize outcomes for affected individuals.
Wang et al. (Thu,) studied this question.