NLRP12-associated autoinflammatory disease: much more than the FCAS phenotype
Clinical and Experimental Rheumatology, cilt.41, sa.10, ss.2115-2121, 2023 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 41 Sayı: 10
- Basım Tarihi: 2023
- Doi Numarası: 10.55563/clinexprheumatol/kzggp3
- Dergi Adı: Clinical and Experimental Rheumatology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CAB Abstracts, EMBASE, Veterinary Science Database
- Sayfa Sayıları: ss.2115-2121
- Anahtar Kelimeler: periodic fever syndrome, systemic autoinflammatory disease, NLRP12, NLRP12-AID, FCAS2
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Objective NLRP12-associated autoinflammatory disease (NLRP12-AID) is a rarely seen periodic fever syndrome also known as familial cold autoinflammatory syndrome-2 (FCAS2), caused by autosomal dominant inherited mutations in the NLRP12 gene. We aimed to present our clinical experience constituting one of the largest paediatric NLRP12-AID cohorts. Methods The patients with preliminary diagnosis of systemic autoinflammatory disease (SAID) other than familial Mediterranean fever (FMF) and PFAPA syndrome were evaluated with the next-generation-sequence (NGS) genetic-panel analysis between January-2016 and January-2022. Among children carrying NLRP12-variant, patients with recurrent episodes of autoinflammatory disease manifestations were diagnosed with NLRP12-AID. Demographic, clinical and laboratory data, treatments and outcomes of patients were presented. Results Seventeen patients were diagnosed with NLRP12-AID. The mean age at diagnosis was 114.7±69.5 months. The most frequently seen clinical manifestations were respectively; fever (100%), arthritis/arthralgia (58.8%), rash (52.9%), abdominal pain (52.9%), diarrhoea (41.2%), myalgia/fatigue (53.2%) and, conjunctivitis (11.7%). Clinical manifestations were triggered by cold exposure in three patients (17.6%). Seven patients had pathogenic, one had likely pathogenic, seven had VUS, and two had novel heterozygous variants. The most common defined variant in the NLRP12 gene was R352C. Complete response was achieved in 5 patients and partial response was in 6 with colchicine treatment. Attacks were prevented with anti-IL-1 treatments in 6 patients unresponsive to colchicine. Conclusion In conclusion, the disease can cause effects on various tissues, especially the musculoskeletal and gastrointestinal systems, apart from FCAS symptoms. We think that a patient who can be defined as syndrome of undifferentiated recurrent fever should also be evaluated genetically in terms of NLRP12 previously.