Unravelling the Genetic Traits Linked to a Refractory Vasculitis: A Case Study on Adenosine Deaminase 2 Deficiency

Abstract

Adenosine deaminase 2 deficiency (DADA2) is a rare genetic disorder that follows an autosomal recessive pattern, stemming from mutations in both copies of the ADA2 gene. This condition leads to reduced enzyme activity and can cause a wide range of issues related to blood vessels, inflammation, and the immune system. We present the case of a 19-year-old male from a family with a history of consanguinity, who has experienced recurrent fevers, mouth sores resembling aphthous ulcers, hives, joint pain due to inflammation, and neurological symptoms that appeared early in life. Imaging of the brain showed several small areas of damage from a lack of blood flow. Lab tests indicated ongoing inflammation without signs of low blood cell counts or deficiencies in immunoglobulins, and tests for infections and immune responses came back negative. Because systemic inflammation can lead to early strokes, we suspected DADA2. Genetic testing confirmed he had a homozygous variant in the ADA2 gene (NM_001282225.2: c.1069G>A). After starting treatment with weekly etanercept, he quickly saw a reduction in fever, stability in his neurological condition, and normalisation of inflammatory markers. This case underscores the importance of considering DADA2 in young patients who show signs of systemic vasculitis, unexplained fevers, or early strokes. Early diagnosis is vital, as prompt anti–TNF-α treatment can help prevent serious complications and greatly enhance patient outcomes.