Patient with Familial Cold Autoinflammatory Syndrome Due to a Mutation in the NLRP3 Gene

Abstract

Introduction: Familial cold autoinflammatory syndrome (FCAS) (MIM120100) is part of the spectrum of hereditary diseases known as cryopyrin-associated periodic syndromes (CAPS). It has an autosomal dominant pattern of inheritance and genetic heterogeneity (FCAS3, FCAS4, NLRC4, NLRP12, NLRP3, and PLCG2). Its prevalence ranges from 2.7 to 5.5 per 1 million. Clinical manifestations typically include early-onset fever, intermittent urticarial rashes, and joint pain occurring 1 to 3 hours after generalized exposure to cold.

Objective: To report a rare clinical case of a patient treated at the Bogotá Society of Surgery Hospital San José (Colombia) with a confirmatory molecular diagnosis of FCAS due to a mutation in the NLRP3 gene.

Methodology: A 27-year-old female patient, the daughter of non-consanguineous parents, presented with clinical symptoms starting in childhood. Her symptoms included a rash associated with itching after exposure to cold, predominantly in the hands and wrists. These symptoms improved with warmth and aspirin. She had a family history of a similar clinical presentation in her deceased mother, two sisters (one of whom had a confirmatory molecular diagnosis), one niece, six maternal aunts, two maternal uncles, and four cousins.

Result: Identification of the NLRP3 genetic variant c.1322 C>T p.Ala441Val in a heterozygous state, which is pathogenic (rs121908146) and associated with FCAS.

Conclusions: The diagnosis of FCAS in our patient was confirmed through the study of a genetic variant previously identified in her sister. The high penetrance of CAPS in this family suggests a high probability of underdiagnosed cases, and this may not be the first case in Colombia but rather the first one to be reported.