Adult-onset vanishing white matter disease due to a novel compound heterozygous EIF2B2 mutation: a case report and brief review

Yuanjing Sun^#^{1

2}, Ruihong Liu^#³, Shujin Tang¹, Yuhua Fan^{4

5}, Jingjing Li^{6

7}

Affiliations

¹ Department of Neurology, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
² Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
³ Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China.
⁴ Department of Neurology, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China. fanyuhua@mail.sysu.edu.cn.
⁵ Department of Neurology and Stroke Center, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, China. fanyuhua@mail.sysu.edu.cn.
⁶ Department of Neurology, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China. lijj7@mail.sysu.edu.cn.
⁷ Department of Neurology and Stroke Center, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, China. lijj7@mail.sysu.edu.cn.

^# Contributed equally.

PMID: 39762463
DOI: 10.1007/s10072-025-07990-6

Adult-onset vanishing white matter disease due to a novel compound heterozygous EIF2B2 mutation: a case report and brief review

Yuanjing Sun et al. Neurol Sci. 2025 Apr.

. 2025 Apr;46(4):1891-1896.

doi: 10.1007/s10072-025-07990-6. Epub 2025 Jan 7.

Authors

Yuanjing Sun^#^{1

2}, Ruihong Liu^#³, Shujin Tang¹, Yuhua Fan^{4

5}, Jingjing Li^{6

7}

Affiliations

¹ Department of Neurology, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
² Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
³ Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China.
⁴ Department of Neurology, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China. fanyuhua@mail.sysu.edu.cn.
⁵ Department of Neurology and Stroke Center, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, China. fanyuhua@mail.sysu.edu.cn.
⁶ Department of Neurology, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China. lijj7@mail.sysu.edu.cn.
⁷ Department of Neurology and Stroke Center, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, China. lijj7@mail.sysu.edu.cn.

^# Contributed equally.

PMID: 39762463
DOI: 10.1007/s10072-025-07990-6

Abstract

Background and objectives: Vanishing white matter disease (VWMD) is an autosomal recessive leukoencephalopathy caused by mutations in the EIF2B1-5 genes, typically rare in adulthood. We present a case of adult-onset VWMD with a novel EIF2B2 mutation.

Methods: We collected the patient's clinical data, cerebrospinal fluid (CSF) results, laboratory tests, imaging features, genetic analysis, and follow-up data over a 4-year period.

Results: A 40-year-old male patient presented with difficulty walking and leg pain. Neurological examination revealed acalculia, slow reaction times, and ataxia. Magnetic resonance imaging (MRI) scans showed diffuse, symmetric lesions with cerebrospinal fluid-like signals predominantly in the subcortical, periventricular, and cerebellar white matter. Genetic testing identified a compound heterozygous mutation in EIF2B2, consisting of a novel nonsense mutation (c.378 T > G, p.Tyr126*) and a reported missense mutation (c.818A > G, p.Lys273Arg) (NM_014239.4).

Discussions: This report highlights the diverse phenotypic manifestations of VWMD and underscores the importance of considering EIF2B2 mutations in adult male patients with bilaterally symmetric hyperintensities in white matter and slowly progressive symptoms.

Keywords: Adult onset; Compound heterozygous mutations; EIF2B2; Vanishing white matter disease.

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Conflict of interest statement

Declarations. Ethical statement: The authors declare that there are no conflicts of interest. The study, which involved human participants, was approved by the Ethics Committee of the Sun Yat-sen University for Human Study and was conducted in accordance with the principles of the 1975 Declaration of Helsinki. The informed and publication consent have been submitted as supplemental material. Competing interests: The authors have no competing interests to declare that are relevant to the content of this article. Conflict of interest: The authors declare that there are no conflicts of interest.

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Adult-onset vanishing white matter disease due to a novel compound heterozygous EIF2B2 mutation: a case report and brief review

Affiliations

Adult-onset vanishing white matter disease due to a novel compound heterozygous EIF2B2 mutation: a case report and brief review

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources