Recurrent Mononeuropathy, Stroke and Deafness in a Teenage Boy

Excerpt

To the Editor: Monogenic autoinflammatory disorders pose a diagnostic challenge due to their variable age of onset and protean manifestations. We report an intriguing case of a 17-y-old boy who began experiencing recurrent neurological symptoms at age 10, starting with an acute-onset left ulnar axonopathy, recovering with antitubercular therapy and steroids. At 15 y, he suffered a brainstem ischemic stroke. Basic stroke workup identified positive anti-nuclear antibodies (1:100 titre, speckled pattern) with rest procoagulant/vasculitis workups being negative. The patient recovered with aspirin and rehabilitative measures within three weeks. A year later, he developed an acute-onset right foot drop (peroneal axonopathy), resolving completely with prednisolone. Ten months later, recurrent acute-onset hearing loss occurred, partially recovering with steroids. Extensive investigations over seven years (Supplementary Fig. S1) including vasculitis workups and digital subtraction angiography, yielded inconclusive results. Suspecting an inherited vasculitis syndrome, whole exome sequencing was sent, which revealed a likely pathogenic, homozygous missense variant (c.139G>C, p.Gly47Arg) in exon 2 of ADA2 gene, confirming the diagnosis of deficiency of adenosine deaminase 2 (DADA2). The patient was started on weekly etanercept and aspirin was discontinued given the risk of hemorrhagic strokes. The patient has been on follow-up for 1 y without experiencing additional flares. …