Mimics and challenging presentations of DADA2

Area of Science:

• Genetics and Immunology
• Rheumatology and Vasculitis
• Rare Disease Diagnosis

Background:

• Deficiency of adenosine deaminase 2 (DADA2), first described in 2014, is characterized by a broad spectrum of clinical presentations.
• The diagnostic challenge stems from its varied phenotypes, including immunological, hematologic, autoinflammatory, and polyarteritis nodosa patterns.
• Existing literature highlights numerous difficult-to-diagnose DADA2 cases, necessitating a consolidated review for clinical practice integration.

Purpose of the Study:

• To review challenging case reports of DADA2 from existing literature.
• To propose an algorithmic approach for diagnosing complex DADA2 presentations.
• To offer expert perspectives and recommendations for clinical management.

Main Methods:

• Comprehensive literature review of challenging DADA2 case reports.
• Analysis of diverse clinical manifestations and diagnostic hurdles.
• Development of a diagnostic algorithm based on integrated findings.

Main Results:

• Summarized diverse and complex DADA2 phenotypes, including immunological, hematologic, autoinflammatory, and adult-onset polyarteritis nodosa.
• Identified key diagnostic challenges and presented an algorithmic approach for suspected cases.
• Emphasized the importance of early diagnosis for preventing severe outcomes.

Conclusions:

• Timely diagnosis of DADA2 is critical to prevent potentially fatal vascular complications, especially with anti-TNF-alpha therapy.
• Early genetic testing, family history evaluation, and thorough clinical assessment are essential for accurate DADA2 diagnosis.
• Enzymatic activity of ADA2, alongside genetic testing and clinical data, serves as a vital diagnostic tool.