Journal Article

Hereditary Transthyretin Amyloidosis in Eight Chinese Families

Ling-Chao Meng He Lyu Wei Zhang Jing Liu Zhao-Xia Wang Yun Yuan

2015

Overview

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 ofmyelinated 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 ofsural 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.

• Publisher: Medknow Publications Pvt Ltd,Medknow Publications and Media Pvt. Ltd,Lippincott Williams & Wilkins Ovid Technologies,Department of Neurology, Peking University First Hospital, Beijing 100034, China,Medknow Publications & Media Pvt Ltd,Wolters Kluwer
• Subject: Adult / Aged / Aged, 80 and over / Amyloid Neuropathies, Familial - diagnosis / Amyloid Neuropathies, Familial - genetics / Amyloidosis / Amyloidosis; Autonomic Nervous Dysfunction; Cardiomyopathy; Sensory-motor Neuropathy; Transthyretin / Arthritis / Asian Continental Ancestry Group / Binding proteins / Biopsy / Constipation / Diarrhea / Female / Gene mutation / Genetic aspects / Health aspects / Humans / Male / Microscopy / Middle Aged / Mutation / Mutation - genetics / Neurology / Original / Patients / Pedigree / Peripheral neuropathy / Prealbumin - genetics / Risk factors / Skin / 中国 / 北京大学第一医院 / 家庭 / 淀粉样变性 / 淀粉样蛋白 / 甲状腺素 / 运载 / 遗传性