{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:56:19Z","timestamp":1777895779938,"version":"3.51.4"},"reference-count":25,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Introduction: Alexander disease (AxD) is a rare neurodegenerative condition that represents the group of leukodystrophies. The disease is caused by GFAP mutation. Symptoms usually occur in the infantile age with macrocephaly, developmental deterioration, progressive quadriparesis, and seizures as the most characteristic features. In this case report, we provide a detailed clinical description of the neonatal type of AxD. Method: Next-Generation Sequencing (NGS), including a panel of 49 genes related to Early Infantile Epileptic Encephalopathy (EIEE), was carried out, and then Whole Exome Sequencing (WES) was performed on the proband\u2019s DNA extracted from blood. Case description: In the first weeks of life, the child presented with signs of increased intracranial pressure, which led to ventriculoperitoneal shunt implementation. Recurrent focal-onset motor seizures with secondary generalization occurred despite phenobarbital treatment. Therapy was modified with multiple anti-seizure medications. In MRI contrast-enhanced lesions in basal ganglia, midbrain and cortico-spinal tracts were observed. During the diagnostic process, GLUT-1 deficiency, lysosomal storage disorders, organic acidurias, and fatty acid oxidation defects were excluded. The NGS panel of EIEE revealed no abnormalities. In WES analysis, GFAP missense heterozygous variant NM_002055.5: c.1187C&gt;T, p.(Thr396Ile) was detected, confirming the diagnosis of AxD. Conclusion: AxD should be considered in the differential diagnosis in all neonates with progressive, intractable seizures accompanied by macrocephaly.<\/jats:p>","DOI":"10.3390\/genes15030350","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T06:05:30Z","timestamp":1710137130000},"page":"350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia\u2014The Neonatal Type of Alexander Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1794-8546","authenticated-orcid":false,"given":"Justyna","family":"Paprocka","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5483-3193","authenticated-orcid":false,"given":"Magdalena","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Machnikowska-Soko\u0142owska","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Radiology and Nuclear Medicine, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6688-2593","authenticated-orcid":false,"given":"Karolina","family":"Rutkowska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical University of Warsaw, 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-5526","authenticated-orcid":false,"given":"Rafa\u0142","family":"P\u0142oski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical University of Warsaw, 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1212\/WNL.0b013e3182309f72","article-title":"GFAP Mutations, Age at Onset, and Clinical Subtypes in Alexander Disease","volume":"77","author":"Prust","year":"2011","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.4103\/1673-5374.369097","article-title":"Alexander Disease: The Road Ahead","volume":"18","author":"Pajares","year":"2023","journal-title":"Neural Regen. 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