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AB0883 Cryopyrinopathy Detected in 10 Family Members of 4 Generations: Importance of Interdisciplinary Collaboration
  1. S. Fingerhutova1,
  2. J. Franova2,
  3. L. Prochazkova3,
  4. P. Dolezalova1
  1. 1Department of Paediatrics and Adolescent Medicine, General University Hospital in Prague, Czech Republic, Prague
  2. 2Department of Paediatric Rheumatology, University Hospital Brno
  3. 3Department of Rheumatology, St Ann's Hospital Brno, University Hospital, Brno, Czech Republic


Background Cryopyrin-associated periodic syndromes (CAPS)are autoinflammatory disorders with autosomal dominant inheritance. Although Muckle-Wells Syndrome (MWS) stands in the middle of theCAPS severity spectrum, it is associated with the high risk of severe late complications that include hearing loss, vision impairment and AA amyloidosis affecting about 26% of individuals. Early diagnosis and appropriate treatment with interleukin-1 (IL-1)blockade may prevent their development

Objectives Analysis of a single paediatric patient trajectory leading to the revelation of multiple members of his family suffering with MWS, description of evolving disease phenotype in patients from different generations. To stress an importance of disease awareness as well as interdisciplinary collaboration in detecting familiar conditions affecting both children and adults.

Methods Multiple-case study.

Results A 3-years old Caucasian boy was referred to the allergologyclinic by his primary care paediatrician for recurrent flares of non-pruritic urticarial rash from about 4 months of age. There were no other symptoms of note. Detailed family history suggested presence of rash in other family members.Working together, paediatric and adult rheumatologist detected additional 9 individuals suffering with variable combinations of fever episodes with rash (all), episodic arthritis, eye inflammation, hearing loss, headache and proteinuria (Graph 1, Table 1). Patient's great grandmother died in 52 years of age from renal failure. Although renal biopsy was not performed at the time, presence of other symptoms as reported by her children made clinical diagnosis of MWS and amyloidosis very likely.

Genetic analysis of exon 3 of NLRP3 gene in affected individuals revealed heterozygous mutation c.1322C>T causing change of amino acids p.Ala441Val and prompted referral to the autoinflammatory disease centre for biologic therapy.

Conclusions In this family medical care was not primarily seeked by adults who have got used to their long-term and relatively mild symptoms. The diagnostic procedure was initiated by the paediatric referral. Detailed analysis of the symptoms suggests presence of the high risk of severe complications. Hearing loss and/or proteinuria have only been noticed in individuals older than 50 years of age. Importantly, younger members below 30 years have not yet developed any of these symptoms which may now be prevented with long-term biologict herapy. This multi-case report illustrates importance of the high degree of suspicion as well as close collaboration between paediatric and adult specialists in order to establish timely diagnosis and initiate appropriate investigations and treatment.

Disclosure of Interest None declared

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