New inflammatory and genetic condition manifesting with recurrent strokes at young age: DADA-2

Case presentation: A 8-year-old girl, born in southeast Brazil, was taken to the neurologist by her parents to investigate repeated unexplained neurological deficits. When she was 4 years old, she presented with livedo reticularis, abdominal pain, fever, and lower digestive hemorrhage. She was extensively investigated, showing increased ESR and RCP, and negative tests for ANA, rheumatoid factor, ANCA, cryoglobulin, antiphospholipid antibody, and serological screening for infectious diseases. This event was interpreted as a possible polyarteritis nodosa (PAN), and treatment with corticoids and azathioprine was prescribed. Despite of treatment, at 7 years old, she presented with focal seizures followed by left hemiparesis, dysarthria, and dysphagia. Three months later, she progressed with right amaurosis, due to ischemic neuritis of the optic nerve; and one year later, with tetraparesis, worse in lower limbs. Her MRI showed midbrain, cerebral peduncles, basal ganglia, and thalamic ischemic lesions of different times of occurrence. Besides, parenchymal microhemorrhages and hemosiderin deposits in right middle temporal gyrus were identified. She did not have any similar history among her family, and her parents were not consanguineous. Considering complete rheumatologic investigation, inflammatory proofs persistently elevated, and vasculopathy involving small and medium-sized vessels, the diagnosis of adenosine deaminase-2 deficiency (DADA2) was plausible. Enzymatic test showed that the patient was deficient in plasma ADA2 activity (0.3mU/g protein; reference: 25–285mU/g protein). Immunosuppressive treatment was prescribed with Adalimumab.

Discussion: DADA-2 is an autoimmune genetic disease, caused by homozygous or compound heterozygous mutations in the CECR1 gene, characterized by vasculopathy in small and medium-sized vessels. Clinical manifestations are stroke in young people, and varied systemic manifestations, such as PAN, livedo reticularis, and recurrent infections.

Final comments: The reported case highlights the importance of considering DADA-2 as a differential diagnosis in patients with PAN symptoms and recurrent neurological deficits at a young age, especially regarding prompt treatment.

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Artikel online veröffentlicht:
18. September 2023