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A previously healthy 19-year-old male born to non-consanguineous parents presented with recurrent, self-limited acute neurological deficits, including ataxia, bilateral internuclear ophthalmoplegia, unilateral facial palsy, contralateral appendicular sensory loss, and non-painful left-eye visual loss. He reported partial recovery, with persistent ophthalmoplegia. These episodes were initially considered autoimmune, and high-dose intravenous corticosteroids were administered. He was referred to our unit with a diagnosis of multiple sclerosis (MS).

On re-examination, he exhibited bilateral internuclear ophthalmoplegia, bilateral sensorineural hearing loss, and livedo reticularis. Laboratory tests showed elevated inflammatory markers. Cerebrospinal fluid analysis was normal, with negative oligoclonal bands. Rheumatologic and infectious workups were unremarkable. Brain MRI revealed perivenular lesions involving the corpus callosum and periventricular white matter. Audiometry confirmed bilateral low and high-frequency sensorineural hearing loss. Visual evoked potentials and fluorescein angiography were normal.

Given atypical features alternative diagnoses were considered, including genetic and autoinflammatory syndromes. Whole genome sequencing identified a pathogenic autosomal recessive variant in the ADA2 gene (NM_001282225.2:c.139G>C; p.Gly47Arg), confirming Adenosine Deaminase 2 Deficiency, a monogenic autoinflammatory disorder with Sneddon-like features.

Autoinflammatory syndromes stem from innate immune dysregulation and often present with systemic inflammation, vasculopathy, and neurologic manifestations—including strokes and sensorineural deficits. The recurrent neurological episodes and brain lesions initially resembled MS, but key differences—bilateral hearing loss, livedo reticularis, negative CSF findings, and rapid onset — raised suspicion for a distinct etiology.

DADA2 can closely mimic MS but requires distinct management. Tumor necrosis factor inhibitors are the mainstay treatment. Acute episodes benefit from anti-inflammatory therapy. The use of antiplatelet or anticoagulant remain controversial due to hemorrhagic risk.

This case underscores the need to consider autoinflammatory diseases in young patients with atypical or multisystem neurological presentations. MS is a frequent initial diagnosis in demyelinating syndromes, but systemic features should prompt further investigation, including genetic testing for rare conditions like DADA2.