Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia—The Neonatal Type of Alexander Disease
Introduction: Alexander disease (AxD) is a rare neurodegenerative condition that represents the group of leukodystrophies. The disease is caused by <i>GFAP</i> mutation. Symptoms usually occur in the infantile age with macrocephaly, developmental deterioration, progressive quadriparesis,...
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MDPI AG
2024-03-01
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| author | Justyna Paprocka Magdalena Nowak Magdalena Machnikowska-Sokołowska Karolina Rutkowska Rafał Płoski |
| author_facet | Justyna Paprocka Magdalena Nowak Magdalena Machnikowska-Sokołowska Karolina Rutkowska Rafał Płoski |
| author_sort | Justyna Paprocka |
| collection | DOAJ |
| description | Introduction: Alexander disease (AxD) is a rare neurodegenerative condition that represents the group of leukodystrophies. The disease is caused by <i>GFAP</i> 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’s 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, <i>GFAP</i> missense heterozygous variant NM_002055.5: c.1187C>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. |
| first_indexed | 2024-04-24T18:15:08Z |
| format | Article |
| id | doaj.art-d2193360baaa4cba835b407a6982202f |
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| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-04-24T18:15:08Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-d2193360baaa4cba835b407a6982202f2024-03-27T13:43:09ZengMDPI AGGenes2073-44252024-03-0115335010.3390/genes15030350Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia—The Neonatal Type of Alexander DiseaseJustyna Paprocka0Magdalena Nowak1Magdalena Machnikowska-Sokołowska2Karolina Rutkowska3Rafał Płoski4Department of Pediatric Neurology, Medical University of Silesia, 40-055 Katowice, PolandDepartment of Pediatric Neurology, Medical University of Silesia, 40-055 Katowice, PolandDepartment of Diagnostic Imaging, Radiology and Nuclear Medicine, Medical University of Silesia, 40-055 Katowice, PolandDepartment of Medical Genetics, Medical University of Warsaw, 02-106 Warsaw, PolandDepartment of Medical Genetics, Medical University of Warsaw, 02-106 Warsaw, PolandIntroduction: Alexander disease (AxD) is a rare neurodegenerative condition that represents the group of leukodystrophies. The disease is caused by <i>GFAP</i> 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’s 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, <i>GFAP</i> missense heterozygous variant NM_002055.5: c.1187C>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.https://www.mdpi.com/2073-4425/15/3/350Alexander diseaseneonatal typerefractory epilepsyleukodystrophysevere hyponatremia |
| spellingShingle | Justyna Paprocka Magdalena Nowak Magdalena Machnikowska-Sokołowska Karolina Rutkowska Rafał Płoski Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia—The Neonatal Type of Alexander Disease Genes Alexander disease neonatal type refractory epilepsy leukodystrophy severe hyponatremia |
| title | Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia—The Neonatal Type of Alexander Disease |
| title_full | Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia—The Neonatal Type of Alexander Disease |
| title_fullStr | Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia—The Neonatal Type of Alexander Disease |
| title_full_unstemmed | Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia—The Neonatal Type of Alexander Disease |
| title_short | Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia—The Neonatal Type of Alexander Disease |
| title_sort | leukodystrophy with macrocephaly refractory epilepsy and severe hyponatremia the neonatal type of alexander disease |
| topic | Alexander disease neonatal type refractory epilepsy leukodystrophy severe hyponatremia |
| url | https://www.mdpi.com/2073-4425/15/3/350 |
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