Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2014 May 15;7(6):3355-62.
eCollection 2014.

An autopsy case of infantile-onset vanishing white matter disease related to an EIF2B2 mutation (V85E) in a hemizygous region

Yukiko Hata  1 , Koshi Kinoshita  1 , Kazushi Miya  2 , Keiichi Hirono  2 , Fukiko Ichida  2 , Koji Yoshida  3 , Naoki Nishida  1
Affiliations
Case Reports

An autopsy case of infantile-onset vanishing white matter disease related to an EIF2B2 mutation (V85E) in a hemizygous region

Yukiko Hata et al. Int J Clin Exp Pathol. .

Abstract

We report a rare autopsy case of early infantile-onset vanishing white matter disease, with a submicroscopic deletion of 14q24.3, which included EIF2B2 and a missense mutation of EIF2B2 (V85E) of the remaining allele. The patient was a 4-year-old boy, who was found to have suddenly died during sleep. Physical and mental development began to deteriorate after convulsions at 10 month of age, and did not recover to baseline measurements. At autopsy, the brain showed a marked decrease in volume of white matter, with no typical cystic rarefaction. Histopathologically, the affected white matter showed diffuse loss of myelin fibers, meager astrogliosis with dysmorphic astrocytes, and loss of oligodendrocytes. Proliferative and apoptotic markers were negative for oligodendrocytes in the severely affected area. These findings may be related to the severity of the disease, and might be a feature of the EIF2B2 mutation pattern of the patient. Additionally, unusual fatty infiltration of both ventricles of the heart was found. These findings were suspected as early pathology of arrhythmogenic right ventricular cardiomyopathy due to characteristic gene mutation in the present case. In the present case, the defect EIF2B2 caused by hemizygosity may be related to early onset of the disease and the unusual pathological changes with vulnerability of oligodendrocytes and astrocytes, as well as cardiac abnormalities and sudden unexpected death.

Keywords: EIF2B2 mutation; Vanishing white matter disease; arrhythmogenic right ventricular cardiomyopathy; hemizygosity; sudden unexpected death.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Coronal sections of the cerebral hemisphere through the mammillary, thalamus, cerebral peduncle, splenium of the corpus callosum, and posterior horn of the lateral ventricle. The white matter is grayish and clearly shows rarefaction. Abbreviations: AC anterior commissure; CC corpus callosum; CP cerebral peduncle; LV lateral ventricle; MB mammillary body; MTN medial thalamic nucleus; PHLV posterior horn of the lateral ventricle; SCC splenium of the corpus callosum.
Figure 2
Figure 2
Pathological findings in the cerebrum, cerebellum, and brainstem of VWMD. The stains used were LFB-H&E (A-E) and Holzer staining (F). (A) Coronal section of the left cerebral hemisphere at the level of the frontal lobe. The white matter is reduced in volume, showing a complete absence of myelin. (B) Coronal section of the left cerebral hemisphere through the thalamus and the cerebral peduncle. Temporal lobes of this patient show widespread loss of myelin and rarefaction of the white matter. Thalami are macroscopically preserved. (C) Transverse section of the midbrain. (D) Transverse section of the medulla oblongata. (E) Transverse section of the cerebellum, including the pons. Myelin fibers running through the cerebral peduncles are severely affected. (F) Gliosis of white matter in the present case was inconspicuous. Abbreviations: CN caudate nucleus; CP: cerebral peduncle; DN: dentate nucleus; EC: external capsule; HC: hippocampus; IC: internal capsule; ICP: inferior cerebellar peduncle; IO: inferior olive; MCP: middle cerebellar peduncle; MRN: medial reticular nucleus; MTN: medial thalamic nucleus; PY: pyramid tract (corticospinal tract); RN: red nucleus; Rn: raphe nucleus; TL: temporal lobe; TPF: transverse pontine fibers; Scale bar for (A-F) 10 mm.
Figure 3
Figure 3
Astrocytes and oligodendrocytes in the white matter from the middle temporal lobe of a VWMD patient (A, C) and normal control (B, D). The stains used were LFB-H&E (A, B) and immunohistochemistry for GFAP (C, D). (A, B) The density of oligodendrocytes was lower in VWMD (A) compared with the control (B). Oligodendrocytes in our VWMD patient show an abnormal appearance. (LFB-H&E staining). A significant increase in astrocytes was not found in the severely affected temporal lobe of the VWMD (C) compared with the control (D). Astrocytes display abnormal morphology with coarse blunt processes in the inset of (C). (Immunohistochemistry for anti-GFAP). Scale bar for (A, B): 40 μm; (C, D): 20 μm.
Figure 4
Figure 4
Microscopic appearance of the heart. (A, B, D) Elastica-Masson staining. (C) H&E staining. (A) Low-power view of the right ventricle. Moderate fibrous replacement of the myocardium is present. (B) High-power view of the right ventricle. (C) Higher magnification of the right ventricle. Mild fatty tissue replacement of the myocardium is present. (D) High-power view of the left ventricle. Moderate fibrous replacement of the myocardium is present. Scale bar for (A): 1 mm; (B): 50 μm; (C): 20 μm; and (D): 100 μm.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Van der Knaap MS, Pronk JC, Scheper GC. Vanishing white matter disease. Lancet Neurol. 2006;5:413–423. - PubMed
    1. Bugiani M, Boor I, Powers JM, Scheper GC, Van der Knaap MS. Leukoencephalopathy with vanishing white matter: A review. J Neuropathol Exp Neurol. 2010;69:987–996. - PubMed
    1. Shimada S, Miya K, Oda N, Watanabe Y, Kumada T, Sugawara M, Shimojima K, Yamamoto T. An unmasked mutation of EIF2B2 due to submicroscopic deletion of 14q24.3 in a patient with vanishing white matter disease. Am J Med Genet A. 2012;158A:1771–1777. - PubMed
    1. Hata Y, Mori H, Tanaka A, Fujita Y, Shimomura T, Tabata T, Kinoshita T, Yamaguchi Y, Ichida F, Kominato Y, Ikeda N, Nishida N. Identification and characterization of a novel genetic mutation with prolonged QT syndrome in an unexplained postoperative death. Int J Legal Med. 2014;128:105–115. - PubMed
    1. Schiffmann R, Fogli A, Van der Knaap MS, Boespflug-Tanguy O. GeneReviews™ [Internet] Seattle (WA): University of Washington, Seattle; 2003. Childhood Ataxia with Central Nervous System Hypomyelination/Vanishing White Matter; pp. 1993–2013. http://www.ncbi.nlm.nih.gov/books/NBK1258/ - PubMed

Publication types

Substances

LinkOut - more resources