{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:39:19Z","timestamp":1786538359050,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373459"],"award-info":[{"award-number":["82373459"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373500"],"award-info":[{"award-number":["82373500"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peroxisomal acyl\u2010CoA oxidase 1 (ACOX1), is a peroxisomal enzyme that catalyzes \u03b2\u2010oxidation of very\u2010long\u2010chain fatty acids (VLCFA). The gain\u2010of\u2010function variant p.Asn237Ser in <jats:italic>ACOX1<\/jats:italic> has been shown to cause Mitchell syndrome (MITCH), a neurodegenerative disorder characterized by episodic demyelination, hearing loss, and polyneuropathy, through the overproduction of hydrogen peroxide. Only eight cases of MITCH have been reported. While all these patients experienced cutaneous abnormalities, detailed skin features and potential treatment have not been documented. Herein, we report two MITCH patients who harbored a de novo heterozygous variant p.Asn237Ser in <jats:italic>ACOX1<\/jats:italic> and experienced progressive ichthyosiform erythroderma. Skin histopathology revealed hyperkeratosis and parakeratosis with focal hypogranulosis as well as dyskeratotic keratinocytes. Lipid accumulation in the epidermis was observed using Oil Red O staining. Both patients exhibited a remarkable response to treatment with the topical antioxidant N\u2010acetylcysteine (NAC), with Patient 1 achieving complete recovery after 3\u2009months of consistent treatment. This study provides the first comprehensive description of the clinicopathological characteristics and effective treatment of skin lesions in MITCH patients. The successful treatment with topical NAC suggests excessive reactive oxygen species might play a significant role in the pathogenesis of skin lesions in MITCH.<\/jats:p>","DOI":"10.1111\/1346-8138.17346","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T12:50:30Z","timestamp":1719233430000},"page":"445-451","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dermatopathological features and successful treatment with topical antioxidant for ichthyosiform lesions in Mitchell syndrome caused by an <scp><i>ACOX1<\/i><\/scp> variant"],"prefix":"10.1111","volume":"52","author":[{"given":"Zhuoqing","family":"Gong","sequence":"first","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"},{"name":"Department of Dermatology Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, National Clinical Research Center for Skin and Immune Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai","family":"Yang","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Ling","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiukuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Zhangzhou Affiliated Hospital of Fujian Medical University  Zhangzhou 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