Novel mutation in the NRLP3 manifesting as an intermediate phenotype of cryopyrinopathies

• Published in: Rheumatology international Vol. 41; no. 1; pp. 219 - 225
• Main Authors: Paim-Marques, Luciana B., Cavalcante, Amanda, Castro, Catherine, Muskardin, Theresa L. Wampler, de Oliveira, João Bosco, Niewold, Timothy B., Appenzeller, Simone
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2021; Springer Nature B.V
• Subjects: Case Based Review; Medicine; Medicine & Public Health; Mutation; Rheumatology; Ulcers; Cryopyrinopathies; NALP3 mutation
• ISSN: 0172-8172; 1437-160X
• DOI: 10.1007/s00296-020-04683-5

Cryopyrin-associated periodic syndromes (CAPS) are a group of autoinflammatory diseases associated with NLRP3 gain of function mutations. CAPS associated mutations are found predominantly in exon 3. The objective of this study is to describe a new variant on NRLP3 gene and its phenotype. Case report description of a new NRLP3 pathogenic variant and literature case-based search through INFEVERS database. A 21-year old male who presented multiple tonic–clonic seizures on his 3rd day of life. At age 2, he had recurrent central facial palsy, high fever (40 °C), painful and persistent oral ulcers, abdominal pain, nausea and vomiting, and delayed neuropsychomotor development, with polyarthritis in wrists and knees. Over the years, several symptoms were observed: livedo reticularis, Raynaud’s phenomenon, positive pathergy test, heat allodynia, extremely painful genital ulcers, and sporadic conjunctivitis. Laboratory studies revealed persistently elevated inflammatory markers and serum amyloid protein A (30 μg/l). The genetic panel for autoinflammatory diseases revealed heterozygous mutation in the NLRP3, (c.2068G > C, p.E690Q) with 0% of frequency in the general population. The patient denies rash and did not have frontal bossing or patellar overgrowth. We found a positive familial history on mother and brother, who carried the same mutation. The patient was started on canakinumab which controlled his symptoms. Currently, 241 missense variants in the NLRP3 have been described. We presented a new mutation in exon 3 of the NRLP3 gene in a patient that fulfills clinical criteria for CAPS who had complete clinical response to Canakinumab, supporting the idea that this mutation is pathogenic.