{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:50:20Z","timestamp":1770771020345,"version":"3.50.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>NAD(P)HX epimerase (NAXE) deficiency is a rare, often fatal, autosomal recessive neurometabolic disorder of early childhood, characterized by acute neurological regression triggered by febrile illness. Here, we report a case with compound heterozygous NAXE mutations (c.733A\u2009&amp;gt;\u2009C and c.389A\u2009&amp;gt;\u2009C) associated with a milder phenotype, thereby expanding the known disease spectrum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case report<\/jats:title>\n                    <jats:p>A previously healthy 19-month-old girl presented with acute neurological regression after a high-grade fever, losing motor skills and exhibiting lethargy. Initial investigations showed leukocytosis, elevated C-reactive protein, and MRI findings of sulcal\/cisternal widening and spinal cord signal changes. Given the unexplained encephalopathy, whole-exome sequencing was performed, which identified compound heterozygous NAXE mutations, confirming the diagnosis. Management included intravenous immunoglobulin, corticosteroids, and NAD\u2009+\u2009precursors. Neurological improvement was observed during the hospital course, and near-complete motor recovery was achieved by the 11-month follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case underscores the need to consider NAXE-related encephalopathy in children with fever-induced acute neurological decline. The discovery of a novel compound heterozygous variant combination [c.389A\u2009&amp;gt;\u2009C [p.His130Pro] and c.733A\u2009&amp;gt;\u2009C [p.Lys245Gln]] defines a milder phenotypic spectrum and mandates early genetic testing for timely diagnosis and prognostic insight. Importantly, given the single-case nature of this observation, conclusion regarding treatment efficacy remains hypothesis-generating and require validation in additional cases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1766864","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T05:27:03Z","timestamp":1770614823000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Progressive encephalopathy associated with novel compound heterozygous NAXE mutations in a Chinese patient: case report and literature review"],"prefix":"10.3389","volume":"14","author":[{"given":"Yanjie","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peifeng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1016\/j.ajhg.2016.07.018","article-title":"NAXE mutations disrupt the cellular NAD(P)HX repair system and cause a lethal neurometabolic disorder of early childhood","volume":"99","author":"Kremer","year":"2016","journal-title":"Am J Hum Genet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.ymgme.2022.04.003","article-title":"NAXE deficiency: a neurometabolic disorder of NAD(P)HX repair amenable for metabolic correction","volume":"136","author":"Manor","year":"2022","journal-title":"Mol Genet 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