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01-04-2022 | Multiple Sclerosis | Original Article

Adult-onset vanishing white matter in a patient with EIF2B3 variants misdiagnosed as multiple sclerosis

Authors: Lulu Xu, Meixiang Zhong, Yuyuan Yang, Meng Wang, Nina An, Xin Xu, Yufeng Zhu, Zengwen Li, Huili Chen, Renliang Zhao, Xueping Zheng

Published in: Neurological Sciences | Issue 4/2022

Abstract

Background

Vanishing white matter (VWM) is an autosomal recessive disorder characterized by childhood ataxia with central hypomyelination. Adult-onset VWM should be considered as a differential diagnosis for suspected cases of multiple sclerosis (MS).

Methods

Targeted region sequencing (TRS) and Sanger sequencing validation were performed to identify and validate the likely pathogenic mutations in a family with VWM.

Results

The main clinical manifestations of the proband included decreased vision and sleepiness accompanied by atrophy of the corpus callosum, affected inner rim of the corpus callosum, decreased apparent diffusion coefficient value or persistent hyperintensity-diffusion-weighted imaging, atrophied optic nerve, and no recordable visual evoked potentials. Due to the slow development and atypical VWM image features, MS was initially suspected. After prednisone was administered, the patient’s condition did not improve significantly, and other diseases were considered. The TRS and Sanger sequencing identified compound heterozygous mutations of EIF2B3 in the proband; c.965C > G /p.Ala322Gly in exon 8 and c.130G > A/p.Glu44Lys in exon 2 were missense mutations inherited from the mother and father, respectively. The proband’s oldest brother had the same compound heterozygous mutations but showed no symptoms.

Conclusion

This is the first report of adult-onset VWM in a Chinese family. Initially, MS was suspected, and genetic testing confirmed the diagnosis of VWM. This study may further broaden the clinical spectrum of EIF2B3, thus providing a foundation for further research on the pathogenesis and genetic therapy for VWM.

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Title: Adult-onset vanishing white matter in a patient with EIF2B3 variants misdiagnosed as multiple sclerosis
Authors: Lulu Xu
Meixiang Zhong
Yuyuan Yang
Meng Wang
Nina An
Xin Xu
Yufeng Zhu
Zengwen Li
Huili Chen
Renliang Zhao
Xueping Zheng
Publication date: 01-04-2022
Publisher: Springer International Publishing
Keywords: Multiple Sclerosis
Leukodystrophy
Published in: Neurological Sciences / Issue 4/2022
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-021-05710-4

At a glance: The STEP trials

Springer Medicine

Adult-onset vanishing white matter in a patient with EIF2B3 variants misdiagnosed as multiple sclerosis

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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