Ann Rehabil Med.  2019 Apr;43(2):234-238. 10.5535/arm.2019.43.2.234.

Correlation Between Vanishing White Matter Disease and Novel Heterozygous EIF2B3 Variants Using Next-Generation Sequencing: A Case Report

• Hyun SE
• Choi BS
• Jang JH
• Jeon I
• Jang DH
• Ryu JS

• KMID: 2449007
• DOI: http://doi.org/10.5535/arm.2019.43.2.234

Abstract

Vanishing white matter (VWM) disease is an autosomal recessive disorder that affects the central nervous system of a patient, and is caused by the development of pathogenic mutations in any of the EIF2B1-5 genes. Any dysfunction of the EIF2B1-5 gene encoded eIF2B causes stress-provoked episodic rapid neurological deterioration in the patient, followed by a chronic progressive disease course. We present the case of a patient with an infantile-onset VWM with the pre-described specific clinical course, subsequent neurological aggravation induced by each viral infection, and the noted consequent progression into a comatose state. Although the initial brain magnetic resonance imaging did not reveal specific pathognomonic signs of VWM to distinguish it from other types of demyelinating leukodystrophy, the next-generation sequencing studies identified heterozygous missense variants in EIF2B3, including a novel variant in exon 7 (C706G), as well as a 0.008% frequency reported variant in exon 2 (T89C). Hence, the characteristic of unbiased genomic sequencing can clinically affect patient care and decisionmaking, especially in terms of the consideration of genetic disorders such as leukoencephalopathy in pediatric patients.

Keyword

Vanishing white matter; Leukoencephalopathies; Genes; Exome

MeSH Terms

Brain
Central Nervous System
Coma
Eukaryotic Initiation Factor-2B
Exome
Exons
Humans
Leukoencephalopathies*
Magnetic Resonance Imaging
Patient Care
White Matter*
Eukaryotic Initiation Factor-2B

Figure

• 

  Fig. 1. Magnetic resonance imaging of brain at the patient’s 20 months old (A, B) and 28 months old (C-F). The T2-weighted image (A, C) shows the diffuse hyperintense abnormality of deep cerebral white matter spreading to whole white matter. The FLAIR image (B, D) shows that more parts of the abnormal white matter have a low signal intensity in (D) than (B), similar to cerebrospinal fluid, indicative of progressive cystic degeneration. Within the abnormal white matter lesion, a pattern of radiating stripes is revealed suggestive of remaining tissue strands. The diffusion weighted image (E) and apparent diffusion coefficient map (F) show restricted diffusion around white matter lesion, indicative of ongoing spreading and active demyelinating process within the white matter.

• 

  Fig. 2. Variants in the EIF2B3 gene in the patient: (A) a novel variant in exon 7 (NM_020365.4: c.706C> G/p.Gln236Glu) and (B) a rare variant in exon 2 (NM_020365.4: c.89T>C/p.Val30Ala).

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