Hereditary transthyretin amyloidosis in mainland China: a unicentric retrospective study

Ann Clin Transl Neurol. 2021 Apr;8(4):831-841. doi: 10.1002/acn3.51328. Epub 2021 Mar 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amyloid Neuropathies, Familial / epidemiology
  • Amyloid Neuropathies, Familial / genetics*
  • Amyloid Neuropathies, Familial / physiopathology*
  • China / epidemiology
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Prealbumin / genetics*
  • Retrospective Studies

Substances

  • Prealbumin
  • TTR protein, human

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related

Grants and funding

This work was funded by Natural Science Foundation grant 7194323; Peking University grant BMU2020PY011.