{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T17:03:56Z","timestamp":1783962236141,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>NAXE\u2010encephalopathy or early\u2010onset progressive encephalopathy with brain edema and\/or leukoencephalopathy\u20101 (PEBEL\u20101) and NAXD\u2010encephalopathy (PEBEL\u20102) have been described recently as mitochondrial disorders causing psychomotor regression, hypotonia, ataxia, quadriparesis, ophthalmoparesis, respiratory insufficiency, encephalopathy, and seizures with the onset being usually within the first three years of life. It usually leads to rapid disease progression and death in early childhood. Anecdotal reports suggest that niacin, through its role in nicotinamide adenine dinucleotinde (NAD) de novo synthesis, corrects biochemical derangement, and slows down disease progression. Reports so far have supported this observation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We describe a patient with a confirmed PEBEL\u20101 diagnosis and report his clinical response to niacin therapy. Moreover, we systematically searched the literature for PEBEL\u20101 and PEBEL\u20102 patients treated with niacin and details about response to treatment and clinical data were reviewed. Furthermore, we are describing off\u2010label use of a COX2 inhibitor to treat niacin\u2010related urticaria in NAXE\u2010encephalopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>So far, seven patients with PEBEL\u20101 and PEBEL\u20102 treated with niacin were reported, and all patients showed a good response for therapy or stabilization of symptoms. We report a patient exhibiting PEBEL\u20101 with an unfavorable outcome despite showing initial stabilization and receiving the highest dose of niacin reported to date. Niacin therapy failed to halt disease progression or attain stabilization of the disease in this patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Despite previous positive results for niacin supplementation in patients with PEBEL\u20101 and PEBEL\u20102, this is the first report of a patient with PEBEL\u20101 who deteriorated to fatal outcome despite being started on the highest dose of niacin therapy reported to date.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmd2.12425","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T05:04:14Z","timestamp":1715317454000},"page":"212-225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Transient response to high\u2010dose niacin therapy in a patient with <scp>NAXE<\/scp> deficiency"],"prefix":"10.1002","volume":"65","author":[{"given":"Fatema","family":"Al\u2010Amrani","sequence":"first","affiliation":[{"name":"Pediatric Neurology Unit, Department of Child Health Sultan Qaboos University Hospital, Sultan Qaboos University  Muscat Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Al\u2010Thihli","sequence":"additional","affiliation":[{"name":"Genetic and Developmental Medicine Clinic, Department of Genetics Sultan Qaboos University Hospital, Sultan Qaboos University  Muscat Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiman","family":"Al\u2010Ajmi","sequence":"additional","affiliation":[{"name":"Department of Radiology and Molecular Imaging Sultan Qaboos University Hospital, Sultan Qaboos University  Muscat Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna","family":"Al\u2010Futaisi","sequence":"additional","affiliation":[{"name":"Department of Child Health College of Medicine and Health Sciences, Sultan Qaboos University  Muscat Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6305-9718","authenticated-orcid":false,"given":"Fathiya","family":"Al\u2010Murshedi","sequence":"additional","affiliation":[{"name":"Genetic and Developmental Medicine Clinic, Department of Genetics Sultan Qaboos University Hospital, Sultan Qaboos University  Muscat Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.07.018"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2022.04.003"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09640-2"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000027548"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy310"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12541"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14631"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760-019-01242-z"},{"key":"e_1_2_13_10_1","unstructured":"DanY FuminYDZ XiaotangC HuiZ YanC. [cited 2023 Jan 31]Clinical and genetic features of progressive early\u2010onset encephalopathy associated with NAXE gene mutation \u2013 PMC. 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