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Vanishing white matter disease: imaging, clinical and molecular correlation in Brazilian families

  • Diagnostic Neuroradiology
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Abstract  

Purpose

To characterize Vanishing White Matter Disease (VWM) cases from a Brazilian University Tertiary hospital, focusing on brain magnetic resonance image (MRI) aspects, clinical and molecular data.

Methods

Medical records and brain MRI of 13 genetically confirmed VWM patients were reviewed. Epidemiological data such as age at symptom onset, gender and main symptoms were analyzed, along with genetic mutations and MRI characteristics, such as the distribution of white matter lesions and atrophy.

Results

The majority of patients were female, with the age of symptom onset ranging from 1 year and 6 months to 40 years. All mutations were identified in the EIF2B5 gene, the most prevalent being c.338G > A (p.Arg113His), and a novel mutation related to the disease was discovered, c.1051G > A (p.Gly351Ser). Trauma or infection were significant triggers. The most frequent symptoms were ataxia and limb spasticity. All MRI scans displayed deep white matter involvement, cystic degeneration, with U-fibers relatively spared and a predilection for the frontoparietal region. Lesions in the corpus callosum and posterior fossa were present in all patients. Follow-up exams revealed the evolution of white matter lesions and cerebral atrophy, which correlated with clinical deterioration.

Conclusions

VWM affects various age groups, with a significant clinical and genetic variability. A novel mutation associated with the disease is highlighted. MRI reveals a typical pattern of white matter involvement, characterized by diffuse lesions in the periventricular and deep regions, with subsequent extension to the subcortical areas, accompanied by cystic degeneration, and plays a crucial role in diagnosis and follow-up.

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Data Availability

I declare the availability of the patient data from this study.

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Acknowledgements

Thanks to Professor Dr. Marjo van der Knaap for the genetic analysis of the patients in this study.

Funding

No funding was received to assist with the preparation of this manuscript.

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Authors and Affiliations

  1. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto – FMRP- USP, R. Ten. Catão Roxo, 3900 - Vila Monte Alegre, Ribeirão Preto, SP, 14015-010, Brazil

    Marianna Angelo Palmejani Albacete, Gustavo Novelino Simão & Antonio Carlos dos Santos

  2. Neurogenetics Unit - Inborn Errors of Metabolism Clinics, National Reference Center for Rare Diseases, Faculdade de Medicina de São José Do Rio Preto, Av. Brigadeiro Faria Lima, - 5416 - Vila São Pedro, São José Do Rio Preto, SP, 15090-000, Brazil

    Charles Marques Lourenço

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  1. Marianna Angelo Palmejani Albacete
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  2. Gustavo Novelino Simão
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  4. Antonio Carlos dos Santos
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Corresponding author

Correspondence to Marianna Angelo Palmejani Albacete.

Ethics declarations

Ethics approval

This project follows resolution CNS 196/96 and was submitted for review by the Research Ethics Committee (CEP) of the Hospital das Clínicas of the Ribeirão Preto Medical School (HCFMRPUSP), obtaining approval under process number 11999/2016. No data collection occurred prior to CEP approval.

Informed consent

The Research Ethics Committee (CEP) of the Hospital das Clínicas of the Ribeirão Preto Medical School (HCFMRP-USP) was requested to waive the need for consent form, given that this is a retrospective study and the present work does not, in any way, alter the course of action already taken regarding the patient's condition. This study solely utilized data from examinations previously conducted at HC-FMRP. Furthermore, we also emphasize that we respect the preservation of absolute anonymity regarding patient information.

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The authors have no competing interests to declare that are relevant to the content of this article.

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Albacete, M.A.P., Simão, G.N., Lourenço, C.M. et al. Vanishing white matter disease: imaging, clinical and molecular correlation in Brazilian families. Neuroradiology (2024). https://doi.org/10.1007/s00234-024-03405-z

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