# Neonatal-onset multisystem inflammatory disease caused by a de novo NLRP3 gene mutation: a case report and literature review

## TL;DR

A newborn with a rare inflammatory disease caused by a new NLRP3 gene mutation showed improvement with canakinumab treatment.

## Contribution

This case report provides insights into the clinical presentation and treatment of neonatal-onset multisystem inflammatory disease with a novel NLRP3 mutation.

## Key findings

- A de novo NLRP3 mutation (c.2263G>A, p.Gly755Arg) was identified in a neonate with multisystem inflammatory symptoms.
- Canakinumab treatment led to rapid resolution of symptoms and sustained remission over 13 months.
- Early genetic diagnosis and targeted IL-1 blockade are critical for preventing complications in NOMID.

## Abstract

Neonatal-onset multisystem inflammatory disease (NOMID) is a rare autoinflammatory disease caused by NLRP3 mutations, leading to excessive interleukin-1β activation and potential irreversible organ damage.

We report a female neonate presenting at birth with urticaria-like rash, intermittent fever, aseptic meningitis, lymphadenopathy, and polyarthritis with persistently elevated inflammatory markers. Whole-exome sequencing revealed a heterozygous de novo NLRP3 mutation (c.2263G>A, p.Gly755Arg), confirmed as pathogenic. Conventional therapies, including antibiotics, corticosteroids, and antihistamines, failed to achieve symptom control. Canakinumab (2–3 mg/kg per 8 weeks) was initiated, leading to rapid resolution of fever, rash, and inflammatory markers, and successful induction of clinical and biochemical remission with canakinumab during the 13-month follow-up.

This case highlights the importance of early recognition of NOMID in neonates with antibiotic-unresponsive systemic inflammation. Early genetic confirmation and targeted IL-1 blockade with canakinumab are crucial to preventing devastating complications.