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CC BY 4.0 · Neuropediatrics
DOI: 10.1055/a-2773-9382
Original Article

Association Between Rapid Progression, Early Mortality, and Imaging in Neonatal-Onset Alexander Disease

Autor*innen

  • Simone Schwarz 

    1   Department of Neonatology and Pediatric Intensive Care Medicine, Sana Clinics Duisburg, Duisburg, Germany
    2   Department of Pediatrics I, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
    3   TNBS, Centre for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

  • Sylke J. Steggerda

    4   Department of Pediatrics, Division of Neonatology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands

  • Linda S. de Vries

    4   Department of Pediatrics, Division of Neonatology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands

  • Katharina Schulz

    5   Clinic for Radiology and Neuroradiology, Sana Clinics Duisburg, Duisburg, Germany

  • Nikola R. Dürr

    5   Clinic for Radiology and Neuroradiology, Sana Clinics Duisburg, Duisburg, Germany

  • Maarten H. Lequin

    6   Department of Radiology, Edward B Singleton, Texas Children's Hospital, Austin, Texas, United States

  • Thorsten Rosenbaum

    7   Department of Pediatrics, Sana Clinics Duisburg, Duisburg, Germany

  • Ursula Felderhoff-Müser

    2   Department of Pediatrics I, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
    3   TNBS, Centre for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

  • Robin-Tobias Jauss

    8   Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

  • Francisco Brevis Nuñes

    1   Department of Neonatology and Pediatric Intensive Care Medicine, Sana Clinics Duisburg, Duisburg, Germany

  • Nora Bruns

    2   Department of Pediatrics I, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
    3   TNBS, Centre for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
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Abstract

Alexander disease represents a rare genetic leukodystrophy caused by abnormal astrocytic accumulations of intracytoplasmic proteinaceous inclusions with astrocyte dysfunction. With neonatal onset, survival ranges from 1.5 months to more than 7.5 years, with a possible association between the underlying point mutation, the level of protein accumulation in the cerebral white matter, disease progression, and survival time. We describe the clinical and cerebral imaging features of a female newborn with neonatal-onset Alexander disease caused by a heterozygous de novo point mutation c.1106T > C; p.(Leu369Pro) located in the coil 2B area of the glial fibrillary acidic protein (GFAP). Early-onset seizures, lethargy, and rapid loss of spontaneous movements were accompanied by rapidly evolving brain morphologic abnormalities and early death. The progression of cerebral abnormalities was monitored by magnetic resonance imaging and serial cranial ultrasound exams. As shown in this case study and the accompanying literature review, rapid accumulation of GFAP, as indicated by volume expansion of affected structures on brain imaging, combined with early onset of seizures and rapid clinical deterioration, seems to be associated with poor prognosis. In this case, high-resolution ultrasound offered an easily accessible, serial bedside imaging tool for the detection and follow-up of pathognomonic features of Alexander disease. We observed a close genotype-phenotype interaction in neonatal-onset Alexander disease, with the c.1106T > C; p.(Leu369Pro) mutation in coil2B associated with early death.

Keywords

neonatal leukodystrophy - neonatal onset - Alexander disease - CUS - white matter disease - neonatal seizures

Data Availability Statement

The datasets supporting the conclusions of this article are included within the article.


Contributors' Statement

S.S. designed the study, carried out data retrieval, extracted literature, interpreted the results, wrote the initial draft, and created figures. L.S.D.V. and S.J.S. scored the CUS images. K.S. and N.R.D. scored the MR images. N.B. carried out statistical analyses, interpreted the results, and revised the initial draft. L.S.D.V., M.H.L., F.B., and T.R. interpreted the patient imaging data regarding the initial diagnosis. J.L. carried out genetic analysis. All authors revised the initial draft and read/approved the final manuscript.


Ethical Approval

The authors adhere to the ethical standards described by the Committee on Publication Ethics and the International Committee of Medical Journal Editors. The infant's parents provided written informed consent for publication.




Publikationsverlauf

Eingereicht: 23. August 2025

Angenommen: 16. Dezember 2025

Artikel online veröffentlicht:
24. Dezember 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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