Genotypic and phenotypic characteristics of juvenile/adult onset vanishing white matter: a series of 14 Chinese patients

Ren, Yuting; Yu, Xueying; Chen, Bin; Tang, Hefei; Niu, Songtao; Wang, Xingao; Pan, Hua; Zhang, Zaiqiang

doi:10.1007/s10072-022-06011-0

Cited by 3 publications

(5 citation statements)

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“…The disease typically presents as a chronic and progressive condition, punctuated by episodes of rapid deterioration following feverish infections or head trauma [ 3 ]. While VWM is probably the most common form of genetic leukoencephalopathy in children, it has become increasingly recognized in adults in recent years [ 5 , 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in any eIF2B variants can impair protein synthesis inhibition and amplify the stress response, potentially explaining the acute neurological deterioration seen after minor head injuries or feverish infections [ 2 ]. Mutations in the EIF2B5 gene are the most prevalent, representing about 56% to 70% of all VWM cases [ 6 , 9 , 10 ]. Additionally, a significant number of adult-onset cases have been linked to mutations in the EIF2B5 gene [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, a significant number of adult-onset cases have been linked to mutations in the EIF2B5 gene [ 11 ]. Mutations in eIF2B3 account for 4% of the mutations reported in patients of European descent, while they represent approximately 29% in the Chinese population [ 6 ]. Moreover, compared to patients of European descent, the incidence of epilepsy in Chinese adult-onset VWM patients is lower, but the incidence of optic neuropathy is higher [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in eIF2B3 account for 4% of the mutations reported in patients of European descent, while they represent approximately 29% in the Chinese population [ 6 ]. Moreover, compared to patients of European descent, the incidence of epilepsy in Chinese adult-onset VWM patients is lower, but the incidence of optic neuropathy is higher [ 6 ]. Nevertheless, it is important to note that the current sample size is relatively small, and larger studies are needed in the future to identify any potential ethnic-specific differences.…”

Section: Discussionmentioning

confidence: 99%

“…Typically, VWM manifests in childhood with symptoms like cerebellar ataxia, moderate spasticity, vision loss, and mild seizures, while cognitive dysfunctions are usually less pronounced. However, there's a growing recognition of VWM in adults [ 5 , 6 ]. Notably, adults with VWM often exhibit more significant cognitive and psychiatric issues compared to the primarily motor disabilities seen in early-onset cases.…”

Section: Introductionmentioning

confidence: 99%

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Adult-onset leukoencephalopathy with vanishing white matter with compound heterozygous EIF2B3 gene variants

Gui,

He,

Qin

2024

BMC Neurol

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Background Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive disorder affecting the white matter of the brain. It typically manifests during childhood, with clinical features including sudden and severe neurological deterioration triggered by stressors such as febrile illness, minor head trauma, or stressful events. Adult-onset cases of VWM are exceptionally uncommon. Case presentation In this case, we present an adult patient who exhibited late-onset progressive VWM characterized by ataxia, postural instability, cognitive impairment, and emotional disturbances. Comprehensive screening for endocrine, metabolic, tumor, and immunologic disorders yielded normal or negative results. Brain imaging revealed diffuse and confluent hyperintensity in the white matter on T2-weighted images, along with periventricular cavitations. Genetic testing confirmed the diagnosis of VWM, identifying two heterozygous variants in the eukaryotic translation initiation factor 2B subunit γ (EIF2B3) gene: a pathogenic variant, c.1037 T > C (p.I346T), and a variant of undetermined significance, c.22A > T (p.M8L). Upon a 2-year follow-up, the patient's symptoms deteriorated rapidly following a COVID-19 infection. Conclusions In conclusion, we have presented a case of classical adult-onset VWM. Since there are no cures or definitive treatments for the disease, it's extremely important to focus on early diagnosis and the prevention of stressors to avoid acute deterioration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adult-onset leukoencephalopathy with vanishing white matter with compound heterozygous EIF2B3 gene variants

Gui,

He,

Qin

2024

BMC Neurol

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Adult-onset leukodystrophy with vanishing white matter: a case series of 19 patients

et al. 2023

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Adult-Onset EIF2B-Pathies: A Clinical, Imaging and Genetic Profiling with Literature Review

Thuppanattumadam Ananthasubramanian,

Arunachal,

Padmanabha

et al. 2024

Can. J. Neurol. Sci.

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Background: Vanishing white matter syndrome is one of the leukoencephalopathies caused by recessive mutations in gene EIF2B1–5. Adult-onset EIF2B-pathies (clinical onset after age 16 years) have been reported to be less common. Objective: Description of the clinical, imaging and genetic profile of adult-onset EIF2B-pathies and comparison of Indian cohort with Asian and European cohorts. Methods: Report of two cases of adult-onset EIF2B-pathies and a comprehensive review of genetically confirmed adult-onset EIF2B-pathies since 2001 from Indian, Asian and European cohorts. Results: Two patients were females, with median age at presentation of 25.5 years (24–27 years) and onset at 19 years (18–20 years). The median duration of symptoms was 6.5 years (6–7 years). Both had cerebellar ataxia, spasticity, cognitive impairment and bladder involvement. Brain magnetic resonance imaging (MRI) showed leukoencephalopathy with rarefaction in both patients and corpus callosum involvement in one patient. Genetics showed homozygous missense variant in the EIF2B3 gene in both patients. The Indian cohort of seven patients had similar clinical and radiological features and common variants in EIF2B3 (n = 4). The Asian cohort had 24 cases, and the European cohort had 61 cases with similar clinical features, radiological features and common variants in EIF2B5. Conclusion: Adult-onset EIF2B-pathies have a distinct clinical profile of female predominance with cerebellar ataxia, spasticity and cognitive decline as the commonest triad of clinical manifestations and leukoencephalopathy with rarefaction on brain MRI. Variants in EIF2B5 were common in the Asian and European cohorts and EIF2B3 in the Indian cohort.

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Genotypic and phenotypic characteristics of juvenile/adult onset vanishing white matter: a series of 14 Chinese patients

Cited by 3 publications

References 54 publications

Adult-onset leukoencephalopathy with vanishing white matter with compound heterozygous EIF2B3 gene variants

Adult-onset leukoencephalopathy with vanishing white matter with compound heterozygous EIF2B3 gene variants

Adult-onset leukodystrophy with vanishing white matter: a case series of 19 patients

Adult-Onset EIF2B-Pathies: A Clinical, Imaging and Genetic Profiling with Literature Review

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