University of Oulu

Knuutinen, O., Kousi, M., Suo-Palosaari, M., Moilanen, J., Tuominen, H., Vainionpää, L., … Vieira, P. (2018). Neonatal Alexander Disease: Novel GFAP Mutation and Comparison to Previously Published Cases. Neuropediatrics, 49(4), 256–261.

Neonatal Alexander disease : novel GFAP mutation and comparison to previously published cases

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Author: Knuutinen, Oula1,2,3; Kousi, Maria4,5; Suo-Palosaari, Maria2,6;
Organizations: 1PEDEGO Research Unit, University of Oulu, Finland
2Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland
3Biocenter Oulu, University of Oulu, Finland
4Folkhälsan Institute of Genetics, Helsinki, Finland
5Center for Human Disease Modeling, Duke University Medical Center, Durham, North Carolina, United States
6Department of Diagnostic Radiology, Oulu University Hospital, Finland
7Department of Clinical Genetics, Oulu University Hospital, Finland
8Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu and Oulu University Hospital, Finland
9Clinic for Children and Adolescents, Oulu University Hospital, Finland
10Neuroscience Center, University of Helsinki, Finland
11Research Programs Unit, Molecular Neurology, University of Helsinki, Finland
12Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
Persistent link:
Language: English
Published: Thieme, 2018
Publish Date: 2019-05-25


Alexander disease (AxD) is a genetic leukodystrophy caused by GFAP mutations leading to astrocyte dysfunction. Neonatal AxD is a rare phenotype with onset in the first month of life. The proband, belonging to a large pedigree with dominantly inherited benign familial neonatal epilepsy (BFNE), had a phenotype distinct from the rest of the family, with hypotonia and macrocephaly in addition to drug-resistant neonatal seizures. The patient deteriorated and passed away at 6 weeks of age. The pathological and neuroimaging data were consistent with the diagnosis of AxD. Genetic analysis of the proband identified a novel de novo GFAP missense mutation and a KCNQ2 splice site mutation segregating with the BFNE phenotype in the family. The GFAP mutation was located in the coil 2B region of GFAP protein, similar to most neonatal-onset AxD cases with an early death. The clinical and neuroradiological features of the previously published neonatal AxD patients are presented. This study further supports the classification of neonatal-onset AxD as a distinct phenotype based on the age of onset.

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Series: Neuropediatrics
ISSN: 0174-304X
ISSN-E: 1439-1899
ISSN-L: 0174-304X
Volume: 49
Issue: 4
Pages: 256 - 261
DOI: 10.1055/s-0038-1649500
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
3124 Neurology and psychiatry
Funding: This work was supported by Folkhälsan Research Foundation.
Copyright information: © 2018 Georg Thieme Verlag KG, Stuttgart · New York