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.

Background and Purpose Autonomic dysfunction is common in transthyretin familial amyloid polyneuropathy (TTR‐FAP). Because ultrasonography is a powerful tool to study peripheral neuropathy, vagus nerve (VN) ultrasonography was used in our study to investigate the possible changes of the dimension of VN in TTR‐FAP. Methods Eighteen patients with TTR‐FAP and 17 age‐ and gender‐matched individuals without any neuropathies were enrolled in a pilot study. The cross‐sectional areas (CSAs) were measured bilaterally on transverse scans of vagus, median, and ulnar nerves. Clinical data were collected to explore the correlations with CSAs of VN. Results The median CSAs of VN in TTR‐FAP were 3.5 (2.0‐6.0) mm2 on the right side and 2.5 (1.0‐6.0) mm2 on the left side, compared with 2.0 (1.0‐3.0) mm2 and 1.0 (1.0‐2.0) mm2 for healthy controls (HCs). There was a significant difference between the two groups on both sides (p < .001). The mean VN CSAs were correlated positively with the course of disease (r = .7203, p = .0016)（not including the patient with the longest disease course), the Composite Autonomic Symptom Score 31 (r = .5252, p = .0252), the left ventricular posterior wall thickness (r = .5426, p = .0200), and the interventricular septum thickness (r = .5103, p = .0305). The cutoff values of right and left VN CSAs to identify TTR‐FAP from HCs were 2.5 and 1.5 mm2 and the areas under the curve were .9395 and .8856, with a high sensitivity (.889 and .889) and specificity (.941 and .765), respectively. Conclusion VN enlargement is prevalent among TTR‐FAP patients. VN ultrasonography may be an important clinical tool for assessing the severity of autonomic dysfunction in TTR‐FAP.

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Backgrounds: Transthyretin familial amyloid polyneuropathy (TTR-FAP) is frequently misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP) because of similar phenotypes in the two diseases. This study was intended to identify the role of nerve ultrasonography in evaluating TTR-FAP and CIDP.Methods: Eighteen patients with TTR-FAP, 13 patients with CIDP, and 14 healthy controls (HC) were enrolled in this study. Consecutive ultrasonography scanning was performed in six pairs of nerves of bilateral limbs with 30 sites. The cross-sectional areas (CSAs) and CSA variability data of different groups were calculated and compared.Results: Both TTR-FAP and CIDP showed larger CSAs at most sites of both upper and lower limbs than in HC groups. CIDP patients had larger CSAs than TTR-FAP patients at 8/15 of these sites, especially at U1-3, Sci2 sites (p &lt; 0.01). However, the CSAs at above sites were not a credible index to differentiate TTR-FAP from CIDP with a low area under the curve (&lt;0.8). The CSA variability of median nerves was significantly higher in CIDP than in TTR-FAP and HC groups, with high sensitivity (0.692) and specificity (0.833) to differentiate CIDP from TTR-FAP. The CSA variability of ulnar nerves was not significantly different between the three groups. For the TTR-FAP group, mean CSAs at each site were not correlated with different Coutinho stages, modified polyneuropathy disability, course of sensory motor peripheral neuropathy, Neuropathy Impairment Score, or Norfolk Quality of life-diabetic neuropathy score. The mean compound muscle action potential of ulnar nerves was negatively correlated with the mean CSAs of ulnar nerves.Interpretation: TTR-FAP patients had milder nerve enlargement with less variability in CSAs of median nerves than those with CIDP, suggesting that nerve ultrasound can be a potential useful auxiliary tool to help differentiate the two neuropathies.

Objective The present study was intended to analyze the characteristics of myelinated nerve fibers density (MFD) of transthyretin amyloid polyneuropathy (ATTR‐PN) and other similar neuropathies. Methods A total of 41 patients with ATTR‐PN, 58 patients of other common peripheral neuropathies, and 17 age‐and gender‐matched controls who visited the First Hospital of Peking University and performed sural nerve biopsy between June 2007 and August 2021 were included for analysis of MFD. Results Except the vasculitic neuropathy group, the total and small MFD of patients in the ATTR‐PN group were significantly lower than those of other disease groups. There was an obvious negative correlation between the total MFD and the disease course in the ATTR‐PN group. The disease course of early‐onset and late‐onset symptoms was similar, but the loss of large myelinated nerve fibers (MF) was more severe for the latter. In addition, all late‐onset and most early‐onset patients had severely reduced MFD after a 2 years' disease course. The MFD in ATTR‐PN patients was negatively correlated with Neuropathy Impairment Score (NIS) and Norfolk Quality of life‐diabetic neuropathy (Norfolk QOL‐DN) score. Conclusion MF is lost differently in ATTR‐PN and in other common peripheral neuropathies. The late‐onset and early‐onset ATTR‐PN patients have different patterns of loss of large and small MF.