We describe Deficiency of Adenosine Deaminase 2 (DADA2) syndrome in two adult siblings of Han Chinese descent in Singapore, who presented with ischemic cerebrovascular disease.

DADA2 syndrome is an inherited, autosomal recessive, autoinflammatory disorder with complex systemic sequelae of varying phenotypes and severity. Vasculitis is a feature, with early-onset strokes as one of its manifestations. The diagnosis is rare, with no cases described in local literature to-date.

The index female patient first presented at the age of 49 with acute left labyrinthitis and lacunar infarcts in the right cerebellar hemisphere. Imaging also revealed chronic silent lacunar infarcts in the right thalamus and left hemipons, with evidence of bilateral vertebral artery vasculitis.

Systemic review demonstrated a long-standing history livedo racemosa, a history of recurrent cutaneous ulcers in her lower limbs, and length-dependent axonal polyneuropathy. Extensive but non-revealing investigations resulted in an initial presumptive diagnosis of Polyarteritis Nodosa, with note made that venous involvement as seen on her skin biopsy would be atypical. Despite good initial response to high doses of steroids, weaning was not possible with therapeutic trials of multiple Disease-Modifying Antirheumatic Drugs.

The brother suffered an episode of amaurosis fugax at age 46, and reported a history of widespread livedo racemosa. He developed his first ulcer, morphologically identical to his sister’s, at age 51.

Upon eventual diagnostic confirmation through low serum ADA2 activity and positive genetic testing, both patients were commenced on adalimumab with excellent clinical response.

Vasculitis as a culprit mechanism is an important consideration in cerebrovascular ischemia, particularly in young patients with suggestive angiographic findings, associated systemic inflammation, or minimal cardiovascular risk factors. Accurate diagnosis of the primary causative syndrome, in these cases DADA2 syndrome, is critical in ensuring patients receive the most efficacious immunosuppressive therapy possible.