Etanercept effectively controls TRNT1-related autoinflammation in patient with homozygous c.1246A>G variant and PCD.

Autoinflammatory syndromes are characterized by recurrent episodes of systemic inflammation without high-titer autoantibodies or antigen-specific T cells. Mutations in the TRNT1 gene, encoding tRNA nucleotidyl transferase 1, are linked to a severe form of autoinflammatory disease, often presenting with early-onset symptoms like fever, arthralgia, and neurological issues. Diagnosing these rare conditions can be challenging, especially when clinical manifestations are atypical or delayed. This case highlights the diagnostic complexity and the need to consider genetic autoinflammatory causes even in patients with co-existing conditions like primary ciliary dyskinesia (PCD), which itself predisposes to chronic respiratory issues and infections.

This is a case report detailing a young woman diagnosed with primary ciliary dyskinesia (PCD) who subsequently developed TRNT1-related autoinflammatory syndrome. The patient presented with recurrent fever and arthralgia starting at age 16. Genetic analysis identified homozygosity for the c.1246A>G variant in the TRNT1 gene, a genotype previously undocumented in this homozygous state. The patient's clinical course and response to treatment were monitored. Etanercept was administered to manage the autoinflammatory symptoms, and its efficacy and safety were observed, particularly given the patient's underlying PCD.

The patient, homozygous for the c.1246A>G variant in the TRNT1 gene, exhibited a milder clinical phenotype compared to previously reported cases with the same variant in a compound heterozygous state. Despite the presence of primary ciliary dyskinesia (PCD), which typically increases the risk of infectious pulmonary complications, Etanercept administration proved highly effective in controlling the autoinflammatory manifestations. > No adverse safety events were observed with Etanercept, demonstrating its tolerability even in a patient with elevated infection risk due to concurrent PCD. This finding is consistent with prior literature on Etanercept's utility in autoinflammatory conditions. The case underscores that TRNT1-related autoinflammatory syndrome can present with delayed onset and milder symptoms, expanding the known phenotypic spectrum associated with this genetic variant.