{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T20:37:03Z","timestamp":1774471023990,"version":"3.50.1"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Ophthal Inflamm Infect"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      ROSAH syndrome (Retinal dystrophy, Optic nerve edema, Splenomegaly, Anhidrosis, and Headache) is a rare autosomal dominant disorder caused by heterozygous missense pathogenic variants in\n                      <jats:italic>ALPK1<\/jats:italic>\n                      . This gene encodes alpha-kinase 1, a key regulator of the inflammatory NF-\u03baB pathway. Pathogenic variants in\n                      <jats:italic>ALPK1<\/jats:italic>\n                      are associated with increased NF-\u03baB activation and chronic inflammation. Clinically, ROSAH syndrome presents with early-onset retinal dystrophy and optic nerve edema, alongside systemic inflammatory and non-inflammatory features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>ALPK1<\/jats:italic>\n                      . 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>ALPK1<\/jats:italic>\n                      in genetic panels for optic neuropathies, retinal disorders, and unexplained arthropathies to improve diagnosis and treatment strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12348-025-00550-1","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T15:23:43Z","timestamp":1763738623000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tocilizumab as a treatment tool for ROSAH syndrome: a case report"],"prefix":"10.1186","volume":"15","author":[{"given":"Rita","family":"Teixeira-Martins","sequence":"first","affiliation":[]},{"given":"Ana","family":"Faria-Pereira","sequence":"additional","affiliation":[]},{"given":"Ana Sofia","family":"Figueiredo","sequence":"additional","affiliation":[]},{"given":"Renata","family":"d\u2019Oliveira","sequence":"additional","affiliation":[]},{"given":"Iva","family":"Brito","sequence":"additional","affiliation":[]},{"given":"Mariana Jorge","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Lu\u00eds","family":"Figueira","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"issue":"4","key":"550_CR1","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.ophtha.2022.10.026","volume":"130","author":"LA Huryn","year":"2023","unstructured":"Huryn LA, Kozycki CT, Serpen JY et al (2023) Ophthalmic manifestations of ROSAH (Retinal dystrophy, optic nerve Edema, Splenomegaly, Anhidrosis, and Headache) Syndrome, an inherited NF kappaB-Mediated autoinflammatory disease with retinal dystrophy. Ophthalmology 130(4):423\u2013432","journal-title":"Ophthalmology"},{"issue":"3","key":"550_CR2","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1002\/ajmg.a.34437","volume":"158A","author":"SK Tantravahi","year":"2012","unstructured":"Tantravahi SK, Williams LB, Digre KB et al (2012) An inherited disorder with splenomegaly, cytopenias, and vision loss. Am J Med Genet A 158A(3):475\u2013481","journal-title":"Am J Med Genet A"},{"issue":"4","key":"550_CR3","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1111\/cge.14286","volume":"103","author":"C Fardeau","year":"2023","unstructured":"Fardeau C, Alafaleq M, Dhaenens CM et al (2023) ROSAH syndrome mimicking chronic uveitis. Clin Genet 103(4):453\u2013458","journal-title":"Clin Genet"},{"issue":"10","key":"550_CR4","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1136\/annrheumdis-2022-222629","volume":"81","author":"CT Kozycki","year":"2022","unstructured":"Kozycki CT, Kodati S, Huryn L et al (2022) Gain-of-function mutations in ALPK1 cause an NF-kappaB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome. Ann Rheum Dis 81(10):1453\u20131464","journal-title":"Ann Rheum Dis"},{"issue":"12","key":"550_CR5","doi-asserted-by":"publisher","first-page":"240260","DOI":"10.1098\/rsob.240260","volume":"14","author":"T Snelling","year":"2024","unstructured":"Snelling T, Garnotel LO, Jeru I et al (2024) Discovery and functional analysis of a novel ALPK1 variant in ROSAH syndrome. Open Biol 14(12):240260","journal-title":"Open Biol"},{"issue":"9","key":"550_CR6","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1038\/s41436-019-0476-3","volume":"21","author":"LB Williams","year":"2019","unstructured":"Williams LB, Javed A, Sabri A et al (2019) ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder. Genet Med 21(9):2103\u20132115","journal-title":"Genet Med"},{"issue":"50","key":"550_CR7","doi-asserted-by":"publisher","first-page":"e2313148120","DOI":"10.1073\/pnas.2313148120","volume":"120","author":"T Snelling","year":"2023","unstructured":"Snelling T, Saalfrank A, Wood NT, Cohen P (2023) ALPK1 mutants causing ROSAH syndrome or spiradenoma are activated by human nucleotide sugars. Proc Natl Acad Sci U S A 120(50):e2313148120","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"550_CR8","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1007\/s10875-020-00741-6","volume":"40","author":"L Zhong","year":"2020","unstructured":"Zhong L, Wang J, Wang W et al (2020) Juvenile onset splenomegaly and oculopathy due to germline mutation in ALPK1. J Clin Immunol 40(2):350\u2013358","journal-title":"J Clin Immunol"}],"container-title":["Journal of Ophthalmic Inflammation and Infection"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12348-025-00550-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12348-025-00550-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12348-025-00550-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T15:23:43Z","timestamp":1763738623000},"score":1,"resource":{"primary":{"URL":"https:\/\/joii-journal.springeropen.com\/articles\/10.1186\/s12348-025-00550-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,21]]},"references-count":8,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["550"],"URL":"https:\/\/doi.org\/10.1186\/s12348-025-00550-1","relation":{},"ISSN":["1869-5760"],"issn-type":[{"value":"1869-5760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,21]]},"assertion":[{"value":"4 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This retrospective review of patient data did not require ethical approval in accordance with national guidelines. Pharmacy and Therapeutics Commission of Unidade Local de Sa\u00fade de S\u00e3o Jo\u00e3o approved tocilizumab use in the patient on June 30, 2024.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the parents\/legal guardian of the patient for publication of the details of their medical case and any accompanying images.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"87"}}