Neuromyelitis optica spectrum disorder in a pediatric patient with ARCN1-related syndrome: A coincidental co-morbidity or disease association?

Background

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare central nervous system autoimmune disease commonly associated with aquaporin-4 antibody (AQP4 Ab). ARCN1-related syndrome is a rare genetic syndrome caused by mutations in archain 1 (ARCN1) gene that encodes the coatomer subunit delta protein in the coat protein complex-I involved in intracellular protein transport. Impaired intracellular trafficking might predispose to autoimmunity. We report a boy with AQP4 Ab positive NMOSD and ARCN1-related syndrome.

Case report

A 7-year-old boy with ARCN1-related syndrome (c.508C>T; p.Arg170*; pathogenic variant) presented with severe right sided optic neuritis, fever, intractable hiccups and vomiting. The patient was diagnosed with NMOSD based on clinical presentation (optic neuritis, area postrema syndrome) and positive AQP4 Ab (serum titer, > 1:100,000). After a 5- day intravenous course of high dose methylprednisolone (30 mg/kg/day), his vision did not improve but other symptoms resolved. Maintenance treatment with intravenous immunoglobulin (IVIG, 0.4 g/kg/monthly) was started, but the patient continued to have recurrent left optic neuritis attacks despite escalating maintenance treatment regimen to oral prednisone in addition to IVIG. At the age of 8, the patient was started on a combination therapy with Rituximab and IVIG and has been NMOSD relapse free since then.

Conclusion

To date, this is the only reported case of NMOSD in a patient with ARCN1 mutation. Our case might further support an increased risk of autoimmunity in carriers of ARCN1 mutation.