Two cases of leukoencephalopathy with vanishing white matter caused by new mutation of EIF2B gene and literature review

doi:10.3969/j.issn.1674-8115.2022.07.018

Abstract

Abstract:

Two cases of leukoencephalopathy with vanishing white matter (VWM) were reported. Patient 1 was a two years and three months old girl whose main clinical manifestation was rapidly progressive motor disturbance following recurrent infections. She developed epilepsy after 6 months. After that, she was unable to walk independently and had difficulty in swallowing. Genetic testing revealed that there were compound heterozygous mutations in the EIF2B4 gene of the proband, including the c.594C>G (p.I98M) in exon 7 inherited from father and the c.1177T>A (p.Y393N) in exon 11 inherited from mother that both had not been reported previously. Cranial MRI showed diffuse symmetrical white matter lesions with prominent white matter thinning. Patient 2 was a 41-year-old female, the second adult VWM case reported in China, mainly manifesting as progressive weakness in both lower limbs and memory loss. Genetic testing revealed that there were compound heterozygous mutations in the EIF2B3 gene of the proband, including the c.130G>A (p.G44K) in exon 2 and the c.934C>G (p.R312G) in exon 8, in which the latter mutation type was reported for the first time. Cranial MRI showed white matter atrophy and ventriculomegaly. Age was a clinical predictor of the severity of VWM, and specifically earlier onset could be associated with more severe disability and higher mortality. Stress was a trigger for the disease and could contribute to neurological deterioration. At present, there is no effective therapy method for this disease. This article reports the two cases, aiming to improve clinicians' understanding of the disease and their ability of early diagnosis, so as to delay the progress of the disease and prolong the survival of the patients.

Key words: leukoencephalopathy with vanishing white matter (VWM), EIF2B gene, epilepsy, infection

CLC Number:

R742.8⁺1

LIU Taotao, WU Jingying, LIU Xiaoli, ZHANG Mei, CAO Li. Two cases of leukoencephalopathy with vanishing white matter caused by new mutation of EIF2B gene and literature review[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(7): 964-970.

Figures/Tables 5

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References 40

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Gene	Number of patients （n=62）/n（%）	Male （n=8）/ n	Female （n=54）/ n	First symptom/n
Gene	Number of patients （n=62）/n（%）	Male （n=8）/ n	Female （n=54）/ n	Cerebellar ataxia （n=39）	Cognitive decline （n=10）	Premature ovarian failure （n=6）	Others （n=7）
EIF2B1	2 （3.2）	1	1	1^［15］	1^［16］	‒	‒
EIF2B2	5 （8.1）	0	5	4^{［10， 17-19］}	1^［11］	‒	‒
EIF2B3	5 （8.1）	0	5	2^{［16， 18］}	0	2^{［8， 20］}	Migraine （n=1）^［21］
EIF2B4	4 （6.4）	0	4	3^{［10， 22］}	1^［18］	‒	‒
EIF2B5	46 （74.2）	7	39	29^{［7-8， 10， 18， 23-25］}	7^{［18， 26-27］}	4^{［8， 10， 18， 23， 28］}	Psychosis （n=4）^{［18， 23， 29-30］}，migraine （n=2）^{［10， 18］}

Gene	Number of patients （n=62）/n（%）	Male （n=8）/ n	Female （n=54）/ n	First symptom/n
Gene	Number of patients （n=62）/n（%）	Male （n=8）/ n	Female （n=54）/ n	Cerebellar ataxia （n=39）	Cognitive decline （n=10）	Premature ovarian failure （n=6）	Others （n=7）
EIF2B1	2 （3.2）	1	1	1^［15］	1^［16］	‒	‒
EIF2B2	5 （8.1）	0	5	4^{［10， 17-19］}	1^［11］	‒	‒
EIF2B3	5 （8.1）	0	5	2^{［16， 18］}	0	2^{［8， 20］}	Migraine （n=1）^［21］
EIF2B4	4 （6.4）	0	4	3^{［10， 22］}	1^［18］	‒	‒
EIF2B5	46 （74.2）	7	39	29^{［7-8， 10， 18， 23-25］}	7^{［18， 26-27］}	4^{［8， 10， 18， 23， 28］}	Psychosis （n=4）^{［18， 23， 29-30］}，migraine （n=2）^{［10， 18］}

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