Mutations in the gene encoding tRNA nucleotidyltransferase 1 (TRNT1) are associated with heterogeneous phenotypes and multisystem involvement of variable severity and progression. Immunodeficiency and inflammation are recurrent-associated features. The use of cytokine inhibitors in suppressing the inflammatory phenotype has been recently reported, with a 3-year follow-up for patients treated with Etanercept. We report on two unrelated patients sharing the same clinical condition, who had been referred to our Pediatric Rheumatology Unit because of recurrent fever associated with cutaneous lesions and increased levels of inflammatory markers since their first months of life. Whole exome sequencing allowed to identify compound heterozygosity for functionally relevant variants in TRNT1 as the only molecular event shared by the two patients. Both patients have been treated with Etanercept during 11 years, documenting normalization of inflammatory indexes and resolution of recurrent fever and associated symptoms. This is the longest follow-up assessment of Etanercept treatment in patients with TRNT1 mutations. Our findings confirm efficacy and safety of the treatment.Key Points• Mutations in TRNT1 have been associated with phenotypic heterogeneity.• We report on two patients with early-onset autoinflammatory syndrome.• Whole exome sequencing led to reveal compound heterozygosity for two variants in TRNT1 in both patients.• The patients were successfully treated with Etanercept for more than 10 years, the longest follow-up described in literature.

Etanercept as a successful therapy in autoinflammatory syndrome related to TRNT1 mutations: a case-based review

Orlando F.;Melis D.;Tartaglia M.;
2021

Abstract

Mutations in the gene encoding tRNA nucleotidyltransferase 1 (TRNT1) are associated with heterogeneous phenotypes and multisystem involvement of variable severity and progression. Immunodeficiency and inflammation are recurrent-associated features. The use of cytokine inhibitors in suppressing the inflammatory phenotype has been recently reported, with a 3-year follow-up for patients treated with Etanercept. We report on two unrelated patients sharing the same clinical condition, who had been referred to our Pediatric Rheumatology Unit because of recurrent fever associated with cutaneous lesions and increased levels of inflammatory markers since their first months of life. Whole exome sequencing allowed to identify compound heterozygosity for functionally relevant variants in TRNT1 as the only molecular event shared by the two patients. Both patients have been treated with Etanercept during 11 years, documenting normalization of inflammatory indexes and resolution of recurrent fever and associated symptoms. This is the longest follow-up assessment of Etanercept treatment in patients with TRNT1 mutations. Our findings confirm efficacy and safety of the treatment.Key Points• Mutations in TRNT1 have been associated with phenotypic heterogeneity.• We report on two patients with early-onset autoinflammatory syndrome.• Whole exome sequencing led to reveal compound heterozygosity for two variants in TRNT1 in both patients.• The patients were successfully treated with Etanercept for more than 10 years, the longest follow-up described in literature.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11386/4803795
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