Unexplained early-onset lacunar stroke and inflammatory skin lesions: Consider ADA2 deficiency

We report 2 brothers who presented at young age with multiple lacunar strokes, inflammatory skin rash, and a range of neurologic symptoms.Case reports.Patient 1 had a history of premature birth, congenital chylothorax, splenomegaly, and chronic anemia post Epstein-Barr virus infection.At age 3 years, he had an episode of lowered consciousness, behavioral regression, and ataxia, with spontaneous recovery within 24 hours.At age 8 years, he experienced speech disturbances, disorientation, left-sided sixth nerve palsy, and right-sided hemiparesis with total recovery after 1 week.MRI revealed a hyperintense lesion in the ventrolateral thalamus, consistent with lacunar infarction (figure , A and B).Magnetic resonance angiography results were normal.On his 11th birthday, he was admitted to the hospital with nausea, vertigo, right-sided hearing loss, and nystagmus.Further clinical details are lacking.The episode was interpreted as labyrinthitis.Repeated MRI showed no new abnormalities.Right-sided hearing loss persisted.A new ischemic left-sided lacunar pontine infarct caused a sixth nerve palsy at age 17 years.Two years later, he developed acute leftsided ptosis, without other abnormalities on physical examination or new imaging findings, which almost completely recovered within 1 month.Ancillary investigations over the years failed to reveal a cardioembolic source or prothrombotic condition.CSF showed an increased leukocyte count.In addition, since 4 years of age, he episodically experienced non-itching red noduli and maculae over his face, arms, and lower legs (figure, D).Skin biopsies revealed deep-reaching angiocentric lymphohistiocytic inflammatory infiltrates, consistent with polyarteritis nodosa (figure, E-G).Immunologic analysis showed no evidence of systemic vasculitis.His younger brother, patient 2, was diagnosed with autism and attention-deficit/hyperactivity disorder.He experienced an acute episode with inability to stand and walk with exotropia of the right eye at age 2 years, without CT abnormalities.All symptoms,