Request Demo

Last update 08 May 2025

Familial Cold Autoinflammatory Syndrome 2

Last update 08 May 2025

Basic Info

Synonyms

FAMILIAL COLD AUTOINFLAMMATORY SYNDROME 2, FCAS2, FCAS2 - familial cold autoinflammatory syndrome type 2

+ [10]

Introduction

An autoinflammatory disease caused by mutations in the NLRP12 gene. It is characterized by periodic fevers beginning in the first year of life that are triggered by cold exposure. Episodes occur more than once per month.

Drugs associated with Familial Cold Autoinflammatory Syndrome 2

Rilonacept

Target

IL-1α x IL-1β

Mechanism

IL-1α inhibitors [+1]

Active Org.

Hangzhou Zhongmeihuadong Pharmaceutical Co., Ltd. [+4]

Originator Org.

Regeneron Pharmaceuticals, Inc.

Active Indication

Muckle-Wells Syndrome [+7]

Inactive Indication

Anemia [+6]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

United States

First Approval Date27 Feb 2008

100 Clinical Results associated with Familial Cold Autoinflammatory Syndrome 2

100 Translational Medicine associated with Familial Cold Autoinflammatory Syndrome 2

0 Patents (Medical) associated with Familial Cold Autoinflammatory Syndrome 2

Literatures (Medical) associated with Familial Cold Autoinflammatory Syndrome 2

01 Aug 2024·Clinical Immunology

NLRP12-associated autoinflammatory disease: A novel causal mutation and bioinformatics analyses

Article

Author: Li, Jiahuang ; Zhu, Bo ; Zhi, Qi ; Li, Zhonghua

Nucleotide-binding leucine-rich repeat-containing receptor 12-associated autoinflammatory disease (NLRP12-AID) is a rare autosomal dominant disorder. In this study, we reported a case of this rare disease with a novel NLRP12 mutation (A218V, rs749659859). The patient displayed typical symptoms, including recurrent fever, arthralgia, and skin allergies. Elevated serum IgE, decreased apolipoprotein A1, high-density lipoprotein cholesterol, and fluctuating levels of various leukocyte subtypes, procalcitonin, IL6, creatine kinase, and 25-hydroxyvitamin D were also detected. Inflammatory lesions were observed in multiple organs using ¹⁸F-FDG PET/CT. By mining single-cell transcriptome data, we identified relatively high expression of NLRP12 in monocytes compared to other human peripheral blood mononuclear cells. NLRP12-positive monocytes exhibited reduced expression of IL18, CCL3, and TNFA compared to NLRP12-negative monocytes. Structural analyses suggested that the A218V mutation, along with A218T and F402L, may reduce the ATP-binding affinity of the NLRP12 protein. These findings may provide new insights into the mechanisms of NLRP12-AID, and suggest the potential ATP-based therapy for further investigation.

01 Dec 2023·RMD Open

NLRP12-associated autoinflammatory disease in Chinese adult patients: a single-centre study

Review

Author: Huang, Xin ; Zhang, Jingyuan ; Miao, Junke ; Wu, Di ; Shen, Min ; Wu, Na

BackgroundNLRP12-associated autoinflammatory disease (NLRP12-AID) is an autosomal dominant autoinflammatory disorder caused by variants ofNLRP12gene. We aimed to report a cohort of Chinese adult patients withNLRP12-AID and summarised phenotypes and genotypes.MethodsTwenty patients were diagnosed withNLRP12-AID after performing whole-exome sequencing and were included in our cohort. Demographic information, clinical data and treatment response were collected and evaluated. A literature review ofNLRP12-AID was performed, and the clinical features and mutated sites were summarised and compared with our cohort.ResultsAmong the 20NLRP12-AID patients, the main clinical features ofNLRP12-AID included fever, cutaneous rash, arthralgia/arthritis, pharyngitis/tonsillitis, lymphadenopathy, myalgia and abdominal pain/diarrhoea. ThirteenNLRP12variants were detected as F402L, G39V, R1030X, R7G, E24A, Q90X, A218V, A259V, W581X, G729R, R859W, c.-150T>C and c.*126G>C. Glucocorticoids were used in 14 patients, immunosuppressive agents in 13, and tocilizumab in 2. Seventeen patients had good responses to therapy. When compared with 50NLRP12-AID patients from other countries, Chinese patients had fewer variants in exon 3, higher incidences of cutaneous rash, pharyngitis/tonsillitis and lymphadenopathy. Among all these 70NLRP12-AID patients, patients carrying non-exon-3 variants had higher frequencies of ocular involvement, pharyngitis/tonsillitis, headache and lymphadenopathy than those with exon-3 variants.ConclusionThis is the largest cohort ofNLRP12-AID in the world and seven novel variants ofNLRP12were identified. Chinese adult patients ofNLRP12-AID had more non-specific symptoms such as pharyngitis/tonsillitis and lymphadenopathy when compared with patients from other countries, for which the less occurrence of exon-3 variants might be one possible reason.

01 Oct 2023·Clinical and experimental rheumatology

NLRP12-associated autoinflammatory disease: much more than the FCAS phenotype.

Article

Author: Sözeri, Betül ; Demir, Ferhat

OBJECTIVESNLRP12-associated autoinflammatory disease (NLRP12-AID) is a rarely seen periodic fever syndrome also known as familial cold autoinflammatory syndrome-2 (FCAS2), caused by autosomal dominant inherited mutations in the NLRP12 gene. We aimed to present our clinical experience constituting one of the largest paediatric NLRP12-AID cohort.METHODSThe patients with preliminary diagnosis of systemic autoinflammatory disease (SAID) other than familial Mediterranean fever (FMF) and PFAPA syndrome were evaluated with the next-generation-sequence (NGS) genetic-panel analysis between January-2016 and January-2022. Among children carrying NLRP12-variant, patients with recurrent episodes of autoinflammatory disease manifestations were diagnosed with NLRP12-AID. Demographic, clinical and laboratory data, treatments and outcomes of patients were presented.RESULTSSeventeen patients were diagnosed with NLRP12-AID. The mean age at diagnosis was 114.7±69.5 months. The most frequently seen clinical manifestations were respectively; fever (100%), arthritis/arthralgia (58.8%), rash (52.9%), abdominal pain (52.9%), diarrhoea (41.2%), myalgia/fatigue (53.2%) and, conjunctivitis (11.7%). Clinical manifestations were triggered by cold exposure in three patients (17.6%). Seven patients had pathogenic, one had likely pathogenic, seven had VUS, and two had novel heterozygous variants. The most common defined variant in the NLRP12 gene was R352C. Complete response was achieved in 5 patients and partial response was in 6 with colchicine treatment. Attacks were prevented with anti-IL-1 treatments in 6 patients unresponsive to colchicine.CONCLUSIONSIn conclusion, the disease can cause effects on various tissues, especially the musculoskeletal and gastrointestinal systems, apart from FCAS symptoms. We think that a patient who can be defined as syndrome of undifferentiated recurrent fever should also be evaluated genetically in terms of NLRP12 previously.

Analysis

Perform a panoramic analysis of this field.

view full example data

Hiro LS Researcher

The AI Search Engine Built to Accelerate Biopharma Decisions

Search across billion-scale life sciences data to uncover signals, validate evidence, and act with confidence.

Ask any biopharma research question→

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, Patsnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Discover Synapse Data Servers

Synapse data is now integrated into the PatSnap LS Model Context Protocol (MCP) service. Customize your LLM agent now using our MCP server!

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Familial Cold Autoinflammatory Syndrome 2

Basic Info

Related

Analysis