27. Cryopyrin associated periodic syndrome (CAPS) with a de novo mutation in NLRP3 gene

Abstract

Background: Cryopyrin associated periodic fever (CAPS) is an auto-inflammatory disorder from mutations in a single gene, NLRP3, encoding a protein called cryopyrin, characterized by periodic attacks of an urticaria like rash, fever, headache, conjunctivitis and arthralgia (1). We report a case of 8-year-old girl with cryopyrin associated periodic syndrome, presenting with papilloedema, chronic anaemia, hearing loss and short stature with a de novo mutation in NLRP3 gene (c.1697>A, Phe566Tyr). Case Presentation: A 8 year old girl with previous history of growth hormone deficiency and Hb D carrier, was referred to the rheumatology department by neurologists with papillodema (raised intracranial pressure), bilateral sensory neural hearing loss, frontal bossing, posterior uveitis, retinitis and slightly enlarged ventricles with thin corpus callosum on imaging. She was also found to have hypermobile joints, with no systemic features of fever, rash, ulcers, lymphadenopathy or organomegaly. The laboratory findings revealed ESR of up to 82mm/h, C-reactive protein 88, elevated serum amyloid A, and raised CSF protein. A genetic analysis showed 2 mutations in NLRP 3 gene (c.1697>A;Phe566Tyr and c.2107C>A;Gln703Lys). A diagnosis of atypical CAPS was made, and patient started on Anakinra (Interleukin-1 receptor antagonist). Following commencement of treatment, there was marked improvement in her acute phase response and improved energy levels with increase in her physical activity. Discussion: The reported patient presented with atypical features of CAPS with elevated acute phase response and mutations in NLRP3 gene. Cryopyrin-associated periodic syndrome (CAPS) is a rare inflammatory disorder with three phenotypes: Familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID). Among them, NOMID type is the severe form presenting with central nervous system involvement and commonly arises from new mutations (2). The clinical manifestations in our reported patient showed predominantly CNS involvement with headache, papilloedema, raised intracranial pressure and sensorineural hearing loss, in keeping with atypical NOMID type and a coexisting new mutation. Learning Points/Conclusion: We report the first case of a child with Phe566Tyr mutation, phenotypically presenting as atypical NOMID type of CAPS with papilloedema, hearing loss and elevated acute phase response. Also in our patient, as previously reported (3), showed marked improvement with Anakinra treatment.