Hereditary Transthyretin Amyloidosis in Eight Chinese Families

Abstract

Background:Mutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis.Methods:Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed.Results:The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2.Conclusions:Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.

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

“…Published estimates for the timing of disease milestones are heavily influenced by patients with Portuguese-type Val30Met disease in endemic countries, which is the most prevalent form and for which onset is typically at 30–40 years old [15], and generally onset is earlier in endemic versus non-endemic countries (except in Sweden where it is typically late-onset). Furthermore, previous case series have reported that age of onset is later for non-Val30Met ATTR-PN [21, 22]. Thus, the later onset reported here appears consistent with the aforementioned trends given that cases were predominantly from non-endemic countries and non-Val30Met (Table 2).…”

Analysis of the TTR gene in the investigation of amyloidosis: A 25-year single UK center experience

“…Untreated disease results in inexorably progressive symptoms with devastating effect on quality of life and reduced survival at 5 to 15 years from the onset of symptoms. ATTRm amyloid deposits within the vitreous causing blindness and the leptomeninges with CNS deficits are also recognized (Connors et al., ; Holmgren, Hellman, Lundgren, Sandgren, & Suhr, ; Long et al., ; Meng et al., ; Uemichi, Uitti, Koeppen, Donat, & Benson, ).…”

Clinical features of familial amyloid polyneuropathy carrying transthyretin mutations in four Chinese kindreds

“…However, TTR‐FAP is now believed to have worldwide distribution (Benson and Kincaid, ) . More and more TTR‐FAP patients in Han Chinese people have been reported (Table ) (Yamamoto et al , ; Chou et al , ; Lachmann et al , ; Li et al , , ; Lim et al , ; Mak et al , , ; Liu et al , , , ; Yang et al , ; Chen et al , ; Zhang et al , , ; Long et al , ; Zou et al , ; Lv et al , ; Meng et al , ) . Here, we identified four different TTR heterozygous mutations already known to be associated with FAP in four unrelated families and among them, mutations Thr49Ala(p.Thr69Ala) and Tyr116Ser(p.Tyr136Ser) were detected for the first time in the Chinese population.…”