A Multicenter Study of Hereditary Transthyretin Amyloidosis in China

Abstract

Objective: Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant genetic disease characterized by the misfolding and deposition of the transthyretin (TTR) protein. This study aimed to describe the clinical and genetic characteristics of ATTRv in a large multicenter Chinese cohort.

Methods: Patients from 14 centers were included in the study. The clinical and genetic characteristics of all patients were summarized. The peripheral blood white blood cell mitochondrial DNA (mtDNA) was detected in offspring from different genders.

Results: A total of 202 individuals with ATTRv from 148 families were identified. The average age of onset was 50.6 ± 12.4 years. Among these cases, 117 (57.9%) were classified as late-onset (≥50 years) and 85 (42.1%) as early-onset. Overall, the length dependent axonal sensorimotor peripheral neuropathy was the predominant phenotype (89.1%). A total of 42 heterozygous missense variants and 1 deletion variant were identified. The most common variants were Val30Met (19.8%) and Ala97Ser (15.8%) and patients with Val30Met and Ala97Ser were mostly late-onset in our cohort. Thirty-nine of these patients died with a mean age of 56.1 ± 13.5 years. Anticipation according to gender groups of offspring-parent pairs was different, and mother-son pairs showed the largest anticipation. The copies of mtDNA in the mother's offspring outnumbered those of the father's offspring (p < 0.001).

Interpretation: This study highlights that ATTRv patients in China exhibit high heterogeneity in their initial symptoms. The most common variants observed in this cohort is Val30Met. The mtDNA copy number shows gender-linked effects. These results can impact ATTRv diagnosis and patient care strategies. ANN NEUROL 2025;97:1158-1167.