J Ophthalmic Inflamm Infect. 2025 Nov 21;15(1):87. doi: 10.1186/s12348-025-00550-1.
ABSTRACT
BACKGROUND: ROSAH syndrome (Retinal dystrophy, Optic nerve edema, Splenomegaly, Anhidrosis, and Headache) is a rare autosomal dominant disorder caused by heterozygous missense pathogenic variants in ALPK1. This gene encodes alpha-kinase 1, a key regulator of the inflammatory NF-κB pathway. Pathogenic variants in ALPK1 are associated with increased NF-κB activation and chronic inflammation. Clinically, ROSAH syndrome presents with early-onset retinal dystrophy and optic nerve edema, alongside systemic inflammatory and non-inflammatory features.
CASE PRESENTATION: We present a 16-year-old female diagnosed with ROSAH syndrome, genetically confirmed. Her clinical course began with subtle abnormalities in her hands by 18 months of age, and by the age of 2 years-old (YO) it was suspected of acquired arthrogryposis and advanced bone age. Around the age of 4YO she was diagnosed with bilateral macular and papillary edema and despite treatment with methotrexate and adalimumab, she continued to experience persistent ocular inflammation and progressive vision loss; hands and feet deformities stopped evolving around age of 6-7YO; at 12YO, due to worsening of macular edema and optic disc swelling, her treatment regimen was modified to include rituximab, which led to modest improvements. Her diagnostic odyssey culminated at 15YO with the identification of the pathogenic variant p.Tyr254Cys in ALPK1. Recently, tocilizumab, an IL-6 receptor antagonist, was added, resulting in significant reduction in macular edema and optic disc swelling just within one month. However, visual function did not improve due to pre-existing retinal damage.
CONCLUSION: Tocilizumab showed significant anatomical benefit in this ROSAH syndrome patient, suggesting a role for IL-6 in disease pathophysiology. Although vision could not be restored, the response supports the use of targeted biologics in managing ROSAH. Broader clinical studies are needed to confirm efficacy. This case also highlights the importance of including ALPK1 in genetic panels for optic neuropathies, retinal disorders, and unexplained arthropathies to improve diagnosis and treatment strategies.
PMID:41269507 | DOI:10.1186/s12348-025-00550-1
