Hereditary autoinflammatory syndromes: a Brazilian multicenter study.

Area of Science:

• Genetics and Immunology
• Rare Diseases
• Clinical Diagnostics

Background:

• Autoinflammatory syndromes (AIS) are a group of rare genetic disorders characterized by recurrent episodes of inflammation.
• Accurate genetic diagnosis is crucial for appropriate management and treatment of AIS.
• Limited data exists on the prevalence of genetic defects in clinically suspected AIS in Brazil.

Purpose of the Study:

• To determine the prevalence of genetic defects in Brazilian patients with suspected autoinflammatory syndromes.
• To evaluate the diagnostic yield of genetic testing for specific AIS subtypes.

Main Methods:

• A multicenter study involving 102 patients with clinical suspicion of AIS.
• Patients were suspected of having Cryopyrin Associated Periodic Syndromes (CAPS), TNF Receptor Associated Periodic Syndrome (TRAPS), Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD), or Pediatric Granulomatous Arthritis (PGA).
• Direct DNA sequencing of key AIS-related genes (NLRP3, TNFRSF1A, MEFV, MVK, NOD2) was performed based on clinical suspicion.

Main Results:

• Of 102 patients, 27 (26.5%) received a confirmed genetic diagnosis.
• Genetic diagnosis rates varied by suspected condition: CAPS (21%), TRAPS (23%), FMF (18%), MKD (18%), and PGA (89%).
• Pediatric Granulomatous Arthritis showed the highest prevalence of confirmed genetic defects.

Conclusions:

• Approximately one-third of Brazilian patients with clinically suspected AIS harbor a confirmed genetic diagnosis.
• Genetic testing is a valuable tool for diagnosing AIS in the Brazilian population.
• Findings underscore the need for increased awareness and genetic investigation of AIS.