Dataset Information

Hyperinsulinaemic hypoglycaemia: A rare association of vanishing white matter disease.

ABSTRACT: We report two unrelated patients with infantile onset leukoencephalopathy with vanishing white matter (VWM) and hyperinsulinaemic hypoglycaemia. To our knowledge, this association has not been described previously. Both patients had compound heterozygous pathogenic variants in EIF2B4 detected on exome sequencing and absence of other variants which might explain the hyperinsulinism. Hypoglycaemia became apparent at 6 and 8 months, respectively, although in one patient, transient neonatal hypoglycaemia was also documented. One patient responded to diazoxide and the other was managed with continuous nasogastric feeding. We hypothesise that the pathophysiology of hyperinsulinism in VWM may involve dysregulation of transcription of genes related to insulin secretion.

SUBMITTER: Bursle C

PROVIDER: S-EPMC7012737 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hyperinsulinaemic hypoglycaemia: A rare association of vanishing white matter disease.

Bursle Carolyn C Yiu Eppie M EM Yeung Alison A Freeman Jeremy L JL Stutterd Chloe C Leventer Richard J RJ Vanderver Adeline A Yaplito-Lee Joy J

JIMD reports 20191112 1

We report two unrelated patients with infantile onset leukoencephalopathy with vanishing white matter (VWM) and hyperinsulinaemic hypoglycaemia. To our knowledge, this association has not been described previously. Both patients had compound heterozygous pathogenic variants in <i>EIF2B4</i> detected on exome sequencing and absence of other variants which might explain the hyperinsulinism. Hypoglycaemia became apparent at 6 and 8 months, respectively, although in one patient, transient neonatal h ...[more]

PMID: 32071834

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

Hyperinsulinaemic hypoglycaemia: A rare association of vanishing white matter disease.

Publications

Hyperinsulinaemic hypoglycaemia: A rare association of vanishing white matter disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure