Tu139 - Deficiency of Human Adenosine Deaminase 2 (DADA2)- the Oxford Experience

Abstract Text: Deficiency of adenosine deaminase type 2 (DADA2) is a rare inherited autoinflammatory condition, first described in 2014, with a prevalence of ~1 in 222,000. It is characterized by systemic vasculitis, stroke, cytopenia, and immunodeficiency. We report three cases from Oxford Clinical Immunology.

Two siblings presented with systemic vasculitis and strokes. The first experienced acute ischaemic infarcts at 11 and 18 years, with no identifiable cause in routine investigations. Whole genome sequencing revealed compound-heterozygous ADA2 mutations: c139G>A (maternal) and c100C>T (paternal). She was initially managed with Aspirin and Inclisiran. Her sister, presenting at 12 years with diplopia and upward gaze nystagmus, was diagnosed with infarcts in the pons and left internal capsule and confirmed to have the same mutations. Immune phenotyping was normal in both, and they are managed with Etanercept for secondary prevention.

A third patient presented at 5 weeks with progressive neutropenia, febrile episodes, recurrent infections, failure to thrive, and microcephaly. Despite normal routine investigations, whole genome sequencing identified homozygous ADA2 exon 7 deletion. Bone marrow aspiration revealed impaired myelopoiesis and maturation. She underwent a bone marrow transplant at 1.5 years with a complex recovery.

These cases highlight the diverse presentations of DADA2 and the diagnostic challenges it poses. A multidisciplinary approach is essential for timely diagnosis and effective management of this rare condition.