Dataset Information

Profile of Indian Children with Childhood Ataxia and Central Nervous System Hypomyelination/Vanishing White Matter Disease: A Single Center Experience from Southern India.

ABSTRACT: Background Childhood ataxia with central nervous system hypomyelination (CACH) is a recently described childhood inherited white matter disease, caused by mutations in any of the five genes encoding eukaryotic translation initiation factor ( eIF2B ). Methods Retrospective review of the charts of children with CACH was performed from January 2014 to March 2020 at tertiary care center from Southern India. Diagnosis was based on magnetic resonance imaging (MRI) criteria or genetic testing. Results Total number of children with CACH enrolled were 18. Male/female ratio was 10:8. Mean age of presentation was 37.11 months (range = 6-144 months). Affected siblings were seen in five (28%) cases. All children had spasticity, ataxia, and diffuse white matter changes with similar signal as cerebrospinal fluid on all pulse sequences on MRI brain. Of the 18 children, only nine are alive. Duration of illness among deceased children was 9.6667 months (range = 2-16 months). Waxing and waning of symptoms were seen in seven cases. Genetic analysis of EIF2B gene was performed in five cases, among which three mutations were novel. Conclusion A diagnosis of childhood ataxia with central nervous system hypomyelination should be considered in patients presenting with acute onset neuroregression following infection or trauma with associated neuroimaging showing classical white matter findings.

SUBMITTER: Gowda VK

PROVIDER: S-EPMC8416235 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Profile of Indian Children with Childhood Ataxia and Central Nervous System Hypomyelination/Vanishing White Matter Disease: A Single Center Experience from Southern India.

Gowda Vykuntaraju K VK Srinivasan Varunvenkat M VM Nagarajan Balamurugan B Bhat Maya M Shivappa Sanjay K SK Benakappa Naveen N

Journal of pediatric genetics 20200727 3

Background Childhood ataxia with central nervous system hypomyelination (CACH) is a recently described childhood inherited white matter disease, caused by mutations in any of the five genes encoding eukaryotic translation initiation factor ( eIF2B ). Methods Retrospective review of the charts of children with CACH was performed from January 2014 to March 2020 at tertiary care center from Southern India. Diagnosis was based on magnetic resonance imaging (MRI) criteria or ge ...[more]

PMID: 34504724

Similar Datasets

Project description:Vanishing white matter (VWM) is a leukodystrophy caused by biallelic pathogenic variants in eukaryotic translation initiation factor 2B. Neuropathology includes lack of reactive gliosis, paucity of myelin, and axonal abnormalities. Alteration in proteins involved in cellular metabolism has also been implicated in the disease. It, however, remains unclear which factors contribute to VWM pathogenesis. Here, we aimed at gaining insight into the basis of VWM pathogenesis using the 2b5ho mouse model of VWM. We first investigated the temporal proteome in the cerebellum, corpus callosum, cortex, and brainstem of 2b5ho and wild type (WT) mice. Protein changes observed in 2b5ho mice were then cross-referenced with published proteomic datasets from post mortem VWM patient brain tissue to define alterations relevant to the human disease. By comparing 2b5ho mice with their region- and age-matched WT counterparts, we identified region-specific protein changes associated with disease development and progression. We showed that the proteome in the cerebellum and cortex of 2b5ho mice was already deregulated prior to pathology development, whereas proteome changes in the corpus callosum only occurred after onset of pathology. Remarkably, protein changes in the brainstem were transient, indicating that a compensatory mechanism might occur in this region throughout the disease course. Gene ontology overrepresentation analysis revealed that proteome changes observed in 2b5ho mouse brains reflect alterations in features well-known in VWM. Side-by-side comparison of the 2b5ho mouse and VWM patient brain proteomes revealed that part of protein changes were the same as in VWM patients. These could represent relevant changes that contribute to the disease or even drive its progression in VWM patients. Taken together, we show that the proteome in the brain of 2b5ho mice is affected in a region-specific and time-dependent manner. We found that the 2b5ho mouse model partly replicates the human disease at the protein level, and provides a spatiotemporal proteome resource to study aspects of VWM pathogenesis. This resource highlights alterations presenting from early to late disease stages, and those that possibly drive disease progression.

Dataset Information

Profile of Indian Children with Childhood Ataxia and Central Nervous System Hypomyelination/Vanishing White Matter Disease: A Single Center Experience from Southern India.

Publications

Profile of Indian Children with Childhood Ataxia and Central Nervous System Hypomyelination/Vanishing White Matter Disease: A Single Center Experience from Southern India.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets