Renal AA amyloidosis associated with a TRAPS-like autoinflammatory phenotype and TNFRSF1A R92Q variant in adulthood

ÇETİN T. E., Haliloglu S., AKÇAY Ö. F., HELVACI Ö., GÜZ G.

Acta Clinica Belgica: International Journal of Clinical and Laboratory Medicine, 2026 (SCI-Expanded, Scopus)

Özet

Background: Tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS) is a rare monogenic autoinflammatory disorder typically presenting with recurrent febrile attacks. However, adult-onset cases without classical inflammatory symptoms may remain unrecognized and can present with organ-dominant manifestations. AA amyloidosis represents a severe complication of chronic inflammation and may be the first clinical manifestation of an underlying autoinflammatory disease. Case Presentation: We report a 48-year-old male with a history of vitiligo who presented with nephrotic syndrome. Renal biopsy confirmed AA amyloidosis. Despite progressive proteinuria and declining renal function, the absence of typical inflammatory symptoms delayed consideration of an autoinflammatory etiology. Empirical anti-inflammatory and biologic therapies, including IL-1 and IL-6 blockade, failed to control disease progression. The patient developed end-stage renal disease and died of septic shock. Post-mortem genetic analysis revealed a heterozygous TNFRSF1A (p.Arg121Gln) variant, supporting a possible atypical adult-onset TRAPS-like autoinflammatory phenotype. Conclusion: This case highlights the diagnostic challenge of TRAPS-like autoinflammatory phenotypes presenting in adulthood without classical inflammatory features, where AA amyloidosis may represent the first clinically apparent manifestation. Autoinflammatory diseases should be considered in adults with unexplained AA amyloidosis after exclusion of secondary causes. However, given the low penetrance and debated pathogenic significance of the TNFRSF1A R92Q variant, the observed genotype–phenotype association should be interpreted cautiously. Earlier recognition of a possible autoinflammatory etiology might offer a theoretical opportunity to limit progressive organ injury; however, whether this would alter outcomes in advanced presentations remains uncertain.