Two Negative Work-ups, One Answer: Unmasking DADA2 a Decade Later
Vibhor Upadhyay1*, Pooja Traipathi2
1Senior Consultant, Neurology, Apollo Hospital, Lucknow, India.
2Senior Consultant, Neurology, Max Hospital, Lucknow, India.
*Corresponding Author: Vibhor Upadhyay,Senior Consultant, Neurology, Apollo Hospital, Lucknow, India.
DOI: https://doi.org/10.58624/SVOANE.2026.07.035
Received: August 04, 2026
Published: September 09, 2026
Citation: Upadhyay V,Traipathi P. Two Negative Work-ups, One Answer: Unmasking DADA2 a Decade Later. SVOA Neurology 2026, 7:5, 273-277. doi. org/10.58624/SVOANE.2026.07.035
Abstract
Background: Deficiency of Adenosine Deaminase 2 (DADA2) is a monogenic vasculopathy caused by biallelic loss-of-function mutations in the ADA2 (formerly CECR1) gene. It classically presents in childhood with polyarteritis nodosa–like vasculitis, livedo racemosa, and recurrent lacunar strokes affecting the deep grey and posterior fossa structures. We report a young man with two temporally distant ischemic strokes, both lacunar and both involving the brainstem, in whom an exhaustive conventional stroke work-up was unrevealing and the diagnosis was ultimately established by whole-exome sequencing.
Case Presentation: A previously healthy male suffered a first ischemic stroke at age 21 years, with imaging localizing the infarct to the medulla. Standard etiological evaluation including cardiac, vascular, haematological, and autoimmune work-up was negative, and the event was labelled cryptogenic. He remained well until age 30, when he presented with a second ischemic stroke, this time localized to the midbrain, again with lacunar morphology. Repeat comprehensive stroke work-up was again negative. Given the recurrent, young-onset, posterior-circulation lacunar stroke pattern with a negative standard evaluation, whole-exome sequencing was pursued and revealed biallelic pathogenic variants in ADA2, confirming a diagnosis of DADA2-associated vasculitis.
Conclusion: This case underscores that DADA2 should be considered in any young patient with recurrent, unexplained lacunar strokes particularly those involving the brainstem even in the absence of the more classically taught cutaneous or systemic vasculitis features. Genetic testing should be incorporated early into the diagnostic algorithm for cryptogenic young-onset stroke, as a specific diagnosis carries direct implications for targeted therapy (anti-TNF agents) and family screening.
Keywords: DADA2, ADA2 Deficiency, Lacunar Infarct, Young-Onset Stroke, Medulla, Midbrain, Monogenic Vasculitis, Cryptogenic Stroke, Whole-Exome Sequencing
