A case report of leukoencephalopathy with vanishing white matter disease (original) (raw)
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Molecular Genetics and Metabolism, 2006
Mutations in eukaryotic initiation factor 2B (eIF2B) cause one of the most common leukodystrophies, childhood ataxia with CNS hypomyelination/vanishing white matter disease or CACH/VWM. Patients may develop a wide spectrum of neurological abnormalities from prenatal-onset white matter disease to juvenile or adult-onset ataxia and dementia, sometimes with ovarian insufficiency. The pattern of diffuse white matter abnormalities on MRI of the head is often diagnostic. Neuropathological abnormalities indicate a unique and selective disruption of oligodendrocytes and astrocytes with sparing of neurons. Marked decrease of asialo-transferrin in cerebrospinal fluid is the only biochemical abnormality identified thus far. Eukaryotic translation initiation factor 2B (eIF2B) mutations cause a decrease in guanine nucleotide exchange activity on eIF2-GDP, resulting in increased susceptibility to stress and enhanced ATF4 expression during endoplasmic reticulum stress. eIF2B mutations are speculated to lead to increased susceptibility to various physiological stress conditions. Future research will be directed towards understanding why abnormal control of protein translation predominantly affects brain glial cells.
Iranian Journal of Pediatrics, 2018
Introduction: Vanishing white matter disease (VWM) is considered as one of the most frequent types of inherited childhood leukoencephalopathies. Various neurological and non-neurological manifestations have been reported in this type of leukodystrophy; however, seizures are rarely described in infantile type of VWM. Case Presentation: To patient is a 12 months old boy who experienced frequent seizures at 4th month of age. The seizures were resistant to anti-epileptic drugs and caused 3 periods of hospitalization. Magnetic resonance imaging (MRI) demonstrated demyelinating pattern and whole exome sequencing (WES) reported homozygous mutation (c.922G > A) in EIF2B2 gene in exon 8 leading to an amino-acid substitution (p.Val308Met). Conclusions: Infantile onset of vanishing white matter disease can be considered as one of few childhood leukodystrophies that are associated with early onset seizures.
Nature Genetics
dren. The course is chronic-progressive with additional episodes of rapid deterioration following febrile infection or minor head trauma. We have identified mutations in EIF2B5 and EIF2B2, encoding the εand β-subunits of the translation initiation factor eIF2B and located on chromosomes 3q27 and 14q24, respectively, as causing VWM. We found 16 different mutations in EIF2B5 in 29 patients from 23 families. We also found two distantly related individuals who were homozygous with respect to a missense mutation in EIF2B2, affecting a conserved amino acid.
Adult-onset vanishing white matter disease presenting as dementia
Annals of Alzheimer's and Dementia Care, 2021
Vanishing White Matter Disease (VWMD), also known as Childhood Ataxia with Central Hypomyelination (CACH) is a leukoencephalopathy with an autosomal recessive inheritance. It is caused by mutations in any of the fi ve genes encoding the fi ve subunits of the eukaryotic translational initiation factor 2B (eIF2B). Although VWMD was initially described in young children, it is now well known that it has a wide phenotypic spectrum, affecting people of all ages. VWMD is typically characterized by normal or mildly delayed initial psychomotor development, followed by episodic or chronic neurological deterioration, often provoked by infections or minor head trauma. Neurological signs consist mainly of cerebellar ataxia and spasticity. There is no specifi c treatment beside the "prevention" of cellular stress. Therefore, early recognition of the diagnosis is important to avoid triggering factors and allow genetic counseling. The reported case describes the clinical and radiological characteristics of a patient with adulthood onset of VWMD, revealed by subcortical dementia.
Vanishing white matter disease with a novel EIF2B5 mutation: A 10-year follow-up
Clinical Neurology and Neurosurgery, 2018
Background: Vanishing white matter disease is a heterogeneous disorder caused by mutation in one of the five genes encoding subunits of the eukaryotic initiation factor eIF2B. It is a heterogeneous disorder due to phenotypic variation and a clear genotype-phenotype correlation could not be established so far. We describe a novel mutation in the EIF2B5 gene by analyzing the clinical phenotype and the progression of brain lesions for 10 years. Case: A novel mutation in the EIF2B5 gene was detected in the heterozygous state; c.1688G > A (p. Arg563Gln) mutation in exon 12, accompanied by a previously detected c.806G > A (p. Arg269Gln) mutation in exon 6, leading to substitution of arginine for a glutamine. This compound heterozygous mutation was associated with disease onset at early childhood and relatively slow progression of neurological deterioration. In contrast to previous findings indicated the association of c.806G > A mutation and peripheral neuropathy in patients with vanishing white matter disease, electromyography of our case was normal. The corpus callosum inner rim was the affected area at early stages, which may be remarkable for early diagnosis of vanishing white matter disease. Serial follow-up magnetic resonance imaging revealed the white matter signal abnormality, subsequently cystic degeneration and decrease in white matter volume. Conclusion: The novel mutation c.1688G > A in compound heterozygous state leads to intermediate phenotype of the vanishing white matter disease. In the early stages of the disease the signal abnormality in the corpus callosum inner rim might be remarkable.
Peripheral neuropathy in vanishing white matter disease with a novel EIF2B5 mutation
Neurology, 2006
The authors describe an infant with vanishing white matter disease with demyelinating peripheral neuropathy. Sequence analysis of EIF2B5 gene showed that the patient was a double heterozygote, with novel missense mutation CGA¡CAA in codon 269 of exon 6, resulting in the replacement of an arginine residue with glutamine.