Epidemiological and clinical characteristics of symptomatic hereditary transthyretin amyloid polyneuropathy: a global case series

Abstract

We describe 542 cases of symptomatic hereditary transthyretin amyloid polyneuropathy (ATTR-PN) identified through a review of the literature published between 2005 and 2016. Approximately 18% of the cases were from countries where ATTR-PN is traditionally considered to be endemic (i.e., Portugal, Japan, and Sweden). East Asia (Japan, China, Taiwan, and South Korea) contributed a sizeable combined proportion (37.0%, n = 200) with Japan (n = 92) and China (n = 71) being the primary contributors. The most common genotypes among the 65 genotypes represented in the sample were Val30Met (47.6%), Ser77Tyr (10%), Ala97Ser (6.5%), and Phe64Leu (4.4%). Cases with genotypes other than the aforementioned four had the lowest ages at onset (mean 49.2 [standard deviation {SD} 21.0; inter-quartile range {IQR}14.7]) and diagnosis (mean 53.4 [SD 21.0; IQR 14.7]). Conversely, Phe64Leu mean age of onset was 67.5 (SD 8.8; IQR 5.2) and mean age of diagnosis was 71.3 (SD 8.8; IQR 5.4). The prevalence of upper and lower limb involvement at the time of diagnosis (67 and 41%) observed across all cases is consistent with the typical presentation of ATTR-PN. Other notable findings at the time of diagnosis included a high rate of impotence among the Ala97Ser cases versus all others (67% vs. 21%) and a high rate of non-motor visual symptoms (i.e., visual opacities and glaucoma) in the Ser77Tyr cases versus all others (93% vs. 16%). Though comparisons were made descriptively and were hindered by inconsistency of reporting across the cases, these findings support the notion that ATTR-PN is a more phenotypically and geographically variable disease than is typically considered.Electronic supplementary materialThe online version of this article (10.1186/s13023-019-1000-1) contains supplementary material, which is available to authorized users.

APOE polymorphism in ATTR amyloidosis patients treated with lipid nanoparticle siRNA

“…More than 100 amyloidogenic mutations of TTR have been described that cause aggregation and amyloid fibril tissue deposition [1]. Clinical presentation of ATTR amyloidosis is diverse and commonly characterised by neurologic and/or cardiac symptoms [2]. After onset of disease, ATTR amyloidosis is associated with premature death ranging from 3 to 10 years.…”

Advances in Treatment of ATTRv Amyloidosis: State of the Art and Future Prospects

“…Hereditary amyloid transthyretin (ATTRv) amyloidosis is a multisystemic disease of adult onset, affecting the sensorimotor nerves, heart, and autonomic function along with other organs such as gastrointestinal tract, eyes, and kidney [ 1 ]. The disease is transmitted with an autosomal dominant pattern, once thought to be restricted to an area of northern Portugal and a few other endemic areas, now documented to be a worldwide disease, with a global prevalence estimated up to 38,000 persons [ 2 , 3 , 4 ]. Early onset, defined as ≤50 years of age at symptom onset, is common in Portugal and Japan, while late-onset cases are predominant in other countries [ 5 , 6 , 7 , 8 ].…”

Impact of Non-Cardiac Clinicopathologic Characteristics on Survival in Transthyretin Amyloid Polyneuropathy

“…ATTR-PN prevalence has been estimated at approximately 10,000 to 40,000 persons globally, with endemic foci in Portugal, Sweden, and Japan [6,7]. Notably, disease phenotypes and penetrance across these endemic areas and elsewhere are often different, even for the same genotype [8]. For example, inaugural symptoms of early-onset disease (\ 50 years old) include spontaneous burning or sharp pain, non-painful sensations (paresthesia and restless leg syndrome), and/or autonomic symptoms (sexual dysfunction, impaired bladder function, constipation alternating with diarrhea, early satiety, orthostatic dizziness and syncope) associated with damaged distal small myelinated and unmyelinated nerve fibers [1].…”