Hereditary transthyretin amyloidosis in mainland China: a unicentric retrospective study

Abstract

Objective This study aims to report the genotypes and phenotypes of hereditary transthyretin amyloidosis (ATTR) in a large Chinese cohort, yet the clinical and genetic profiles of ATTR remain elusive in mainland China. Methods Fifty‐four patients with molecularly confirmed ATTR from 39 unrelated families were identified by sequencing the TTR gene. Sural nerve biopsies were performed in 40 of these cases. The clinical and electrophysiological data were retrospectively collected and analyzed. Results The male/female ratio was 42:12. The average age of patients at the onset of the disease was 47.8 ± 13.0 years. The late‐onset type occurred in 29 cases (53.7%). Twenty‐two probands (56.4%) had a family history with ATTR. The initial symptoms were limb paresthesia in 33 cases (61.1%), autonomic dysfunction in 15 cases (27.8%), and blurred vision in 6 cases (11.1%). A total of 22 different TTR mutations were identified, including Val30Met (25.6%) in 10 families in North China and Ala97Ser in 4 families (10.3%) in South China. Electrophysiological studies revealed general sensorimotor axonal polyneuropathy in 33/44 cases (75.0%), mixed neuropathy with axonal and demyelinating impairment features in 9/44 cases (20.5%) and isolated carpal tunnel syndrome in two cases. Sural nerve biopsies revealed positive Congo red staining in 16/40 cases (40.0%). Conclusion Chinese patients with ATTR exhibited heterogeneous TTR genotypes and clinical phenotypes. Val30Met remains the most common mutation type in mainland China.

GGC Repeat Expansion in the NOTCH2NLC Gene Is Associated With a Phenotype of Predominant Motor–Sensory and Autonomic Neuropathy

“…More importantly, patients in our cohort had much severe autonomic neuropathy such as bladder dysfunction and constipation, which is very rare in classical CMT ( Laurá et al, 2019 ). While 90.7% of the patients with TTR-FAP showed autonomic dysfunction mainly presenting as gastrointestinal involvement including alternative diarrhea and constipation, orthostatic hypotension and urinary dysfunction, however, were reported in only 27.8% of TTR-FAP patients ( Du et al, 2021 ). Our findings indicated that NOTCH2NLC -related IPN was a distinct phenotype of hereditary polyneuropathy.…”

“…Inherited peripheral neuropathy (IPN) represents a large heterogenous group of hereditary diseases including hereditary motor and sensory neuropathy (HMSN), more commonly called Charcot–Marie–Tooth disease (CMT), hereditary sensory and autonomic neuropathy (HSAN), distal hereditary motor neuropathy (dHMN), and small fiber neuropathies (SFN) ( Schröder and Matthiesen, 1985 ; Eggermann et al, 2018 ). There are also other forms of IPN such as transthyretin familial amyloid polyneuropathy (TTR-FAP), a severe hereditary neuropathy affecting the sensorimotor and autonomic function as well as other organs caused by mutation of the TTR gene ( Adams et al, 2017 ; Du et al, 2021 ). With the development of next-generation sequencing (NGS) technologies, including disease-target gene panels, whole-exome sequencing (WES), whole-genome sequencing (WGS), and high-throughput transcriptome sequencing, more than 100 and 30 genes have been associated with CMT and dHMN, respectively ( Laurá et al, 2019 ; Pipis et al, 2019 ; Liu et al, 2020 ).…”

Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort

“…ATTRA97S is mostly endemic in Taiwan (Han-Taiwanese) with male predominance [7][8][9][10]. It is also a common TTR mutation in mainland China (Han-Chinese), particularly in southern China [17][18][19][20]. One study from Malaysia reported ATTRA97S-PN in nine Chinese Malaysian patients [21].…”

“…Additionally, symptomatic patients were not restricted to late adulthood and elderly individuals. Patients' symptoms may start in their early 30 s. A review of the English literature in the PubMed search engine revealed 12 clinical studies with clinical data (including case reports) of ATTRA97S-PN [6][7][8][9][10][17][18][19][20][21][22][23]. The first case was reported in 1999 [23].…”

“…The first case was reported in 1999 [23]. Additional file 2 shows the epidemiologic data and clinical features of Thai patients in comparison to those in 12 previous reports [6][7][8][9][10][17][18][19][20][21][22][23].…”