Mystery of the Vanishing Diplopia: A Relapsing Neurologic Puzzle in an Adolescent

Document Type

Conference Proceeding

Publication Date

8-2026

Abstract

Initial History/Presentation: A previously healthy 12-year-old female presented with recurrent admissions over 11 months with intermittent diplopia, headaches, vertigo, and focal weakness.

Physical Exam: Initial examination revealed right internuclear ophthalmoplegia (INO). With subsequent admissions, she developed INO and ptosis of alternating laterality, intermittent facial weakness, and transient gait instability. Papilledema was never noted.

Diagnostic Evaluation: Initial evaluation revealed elevated inflammatory markers but otherwise unremarkable laboratory testing, brain imaging, and cerebrospinal fluid (CSF) studies. She was initially diagnosed with post-infectious INO and treated with 5 days of prednisone, resulting in rapid improvement. Seven months later, she developed evolving neurologic symptoms with systemic manifestations. Serial brain MRI studies demonstrated progressive and expanding diffusion-restricted lesions, raising concern for a demyelinating disease versus ischemia. She developed abdominal pain and palpable purpura of the bilateral lower extremities with hematuria and proteinuria, leading to the consideration of IgA vasculitis; however, biopsy of skin lesions was consistent with erythema nodosum. Comprehensive serum and CSF testing for autoimmune, vasculitic, demyelinating, infectious (including fungal and venereal), malignant, and inflammatory etiologies remained unrevealing. On her final admission, she developed acute right facial droop with right upper and lower extremity weakness. Repeat brain MRI demonstrated findings most consistent with an ischemic stroke.

Diagnosis: With concern for systemic vasculitis with central nervous system (CNS) involvement, ADA2 activity was tested and undetectable. Confirmatory single ADA2 gene sequencing showed a homozygous pathogenic variant, and she was diagnosed with deficiency of ADA2 (DADA2) and started on etanercept therapy.

Discussion/Conclusion: ADA2 is an enzyme crucial for maintaining blood vessel wall integrity, directly or indirectly. DADA2 is a rare, autosomal recessive, autoinflammatory disease that can present with systemic inflammation and vasculitis. Symptomology varies among genotypes and there is variable expressivity. Symptom onset is typically before the age of 10 years with involvement of the CNS (stroke), skin (livedo racemosa, subcutaneous nodules), visceral organs (infarction, hemorrhage), hematopoiesis (bone marrow failure), and/or immune system (hypogammaglobulinemia). Tumor necrosis factor inhibitors are the mainstay of treatment of the vascular subtype with stem cell transplant reserved for severe or refractory cases.

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Pediatric Hospital Medicine Conference, August 6-9, 2026, Kansas City, MO

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