NLRP3 E311K mutation in a large family with Muckle-Wells syndrome - description of a heterogeneous phenotype and response to treatment

• DOI: 10.1186/ar3526
• Publication Date: 2011-12-06T19:24:00Z
• Authors: Jasmin B Kuemmerl...; Peter Lohse; Ina Koetter; Guenther E Dannecker; Fabian Reess; Katharina Ummenhofer; Silvia Koch; Nikolay Tzaribachev; Anja Bialkowski; Susanne M Benseler
• Keywords: Canakinumab; Erythrocyte sedimentation rate; AA amyloidosis

Muckle-Wells syndrome (MWS) is an inherited autoinflammatory disease characterized by fever, rash, arthralgia, conjunctivitis, sensorineural deafness and potentially life-threatening amyloidosis. The NLRP3/CIAS1 E311K mutation caused a heterogeneous phenotype of MWS in large family. This study analyzes the clinical spectrum, patterns inflammatory parameters reports on response to treatment.A total 42 patients family members were screened for presence NLRP3 mutation. Clinical symptoms reviewed all members. Classical (erythrocyte sedimentation rate (ESR, C-reactive protein (CRP)) novel markers (serum amyloid A (SAA), cytokines, cytokine receptor levels) determined. Patients treated with IL-1 inhibitors Anakinra or Canakinumab.All 13 clinically affected heterozygous carriers amino acid substitution p.Glu311Lys/E311K encoded exon 3 gene, but none healthy Disease manifestations varied widely. Except one child, suffered from hearing loss severe fatigue. TNF-α, IL-6, TNF-RI, TNF-RII levels as well SAA elevated three, two, one, six ten patients, respectively. Both laboratory responded quickly sustainedly treatment Canakinumab.The associated which may expand view presentation. leading symptom was loss. Pericarditis, rare feature MWS, diagnosed three patients. One patient had course, led renal failure secondary inhibition leads rapid sustained improvement symptoms.