International Journal of Nutrition, Pharmacology, Neurological Diseases

: 2013  |  Volume : 3  |  Issue : 4  |  Page : 396--397

Fatal vanishing white matter disease with unexplained hypertension due to E1F2B5 homozygous mutation

Yusuf Parvez1, Nawal Maksheed2, Osama Shalabi3, Sateesh Kalanthra Kutty4,  
1 Department of Pediatrics, Al-Jahra Hospital, Kuwait
2 Department of Pediatrics and Metabolic Disease, Al-Jahra Hospital, Kuwait
3 Department of Neurology, Al-Jahra Hospital, Kuwait
4 Department of Pediatrics, Pediatric Intensive Care Unit, Al-Jahra Hospita, Kuwait

Correspondence Address:
Yusuf Parvez
Department of Pediatrics, Pediatric Intensive Care Unit, Al-Jahra Hospital, PO Box 40206


Vanishing white matter is an autosomal recessive leukoencephalopathy linked to mutations in the eukaryotic translation initiation factor 2B. It is a disease of infants, children and adults who experience a slowly progressive neurologic deterioration with episodes of rapid clinical worsening and eventually leading to death. We report a classical case to highlight its clinical significance.

How to cite this article:
Parvez Y, Maksheed N, Shalabi O, Kutty SK. Fatal vanishing white matter disease with unexplained hypertension due to E1F2B5 homozygous mutation.Int J Nutr Pharmacol Neurol Dis 2013;3:396-397

How to cite this URL:
Parvez Y, Maksheed N, Shalabi O, Kutty SK. Fatal vanishing white matter disease with unexplained hypertension due to E1F2B5 homozygous mutation. Int J Nutr Pharmacol Neurol Dis [serial online] 2013 [cited 2020 Jul 6 ];3:396-397
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Full Text


Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive hereditary disease presenting with progressive deterioration in neurological status. Characteristic neuropathologic findings include cystic degeneration of the white matter with scarce reactive gliosis, dysmorphic astrocytes and paucity of myelin despite an increase in oligodendrocytic density.

 Case Report

A 4-month-old previously healthy Kuwait boy, product of consanguineous parents, full-term normal delivery with uneventful neonatal period was admitted to our hospital with a history of the first episode of generalized tonic-clonic convulsions for 2-3 min followed by drowsiness. Patient was admitted to the ward and developed another episode of convulsions subsided by diazepam. There was no history of fever or head trauma. On examination, patient was found to be spastic and less active. His other systemic examination was unremarkable. Urgent computed tomography of the brain showed diffuse accentuated white matter hypodensity. Magnetic resonance imaging (MRI) of the brain revealed abnormal hypointense signal of the deep white matter with lack of normal myelination [Figure 1]. Based on the clinical and radiological findings, metachromatic leukodystrophy or krabbe's diseases were suspected initially, but genetic study and enzyme studies were against the diagnosis. Patient was investigated further to rule out other possibilities. His basic metabolic work was unremarkable. Electroencephalogram showed prolonged frontotemporal electrographic seizures. Fundus examination revealed optic atrophy. His serial MRI brain showed extensive abnormality of white matter with cystic degeneration suggestive of VWM disease. Patient was found to have homozygous mutation in E1F2B5 gene confirming the diagnosis of VWM disease. He was managed symptomatically along with anticonvulsants. Patient developed unexplained hypertension probably due to vasomotor instability during the 2 nd week of hospital stay and was controlled with clonidine. He was investigated thoroughly for the cause of hypertension, including renal Doppler, echocardiogram and endocrinal work-up. However, the results were inconclusive. Patient deteriorated progressively and became comatosed subsequently. He was given palliative care, but succumbed to death at the age of 1½ year.{Figure 1}


VWM disease is a progressive leukoencephalopathy affecting infants, children and adults. [1] The phenotypic variation is extremely wide, including antenatal onset and early demise and adult-onset, slowly progressive disease. The basic defect of this disease lies in one of the five subunits of eukaryotic translation initiation factor E1F2B. [2],[3] Leukoencephalopathy with VWM is a progressive disorder that mainly affects the brain and spinal cord (central nervous system). This disorder causes deterioration of the central nervous system's white matter. In most cases, people with leukoencephalopathy with VWM show no signs or symptoms of the disorder at birth. Affected children may have slightly delayed development of motor skills such as crawling or walking. During early childhood, most affected individuals begin to develop motor symptoms, including abnormal muscle stiffness (spasticity) and difficulty with coordinating movements (ataxia). There may also be some deterioration of mental functioning. MRI of the brain is diagnostic indicative of VWM. MRI generally shows diffuse abnormality of the cerebral white matter, which becomes increasingly rarefied and cystic. [4],[5] The association of hypertension with VWM has not been described yet as per the existing literature. The outcome is fatal in all cases of this entity.


1van der Knaap MS, Pronk JC, Scheper GC. Vanishing white matter disease. Lancet Neurol 2006;5:413-23.
2Wu Y, Pan Y, Du L, Wang J, Gu Q, Gao Z, et al. Identification of novel EIF2B mutations in Chinese patients with vanishing white matter disease. J Hum Genet 2009;54:74-7.
3Alsalem A, Shaheen R, Alkuraya FS. Vanishing white matter disease caused by EIF2B2 mutation with the presentation of an adrenoleukodystrophy phenotype. Gene 2012;496:141-3.
4van der Lei HD, Steenweg ME, Barkhof F, de Grauw T, d'Hooghe M, Morton R, et al. Characteristics of early MRI in children and adolescents with vanishing white matter. Neuropediatrics 2012;43:22-6.
5Bugiani M, Boor I, van Kollenburg B, Postma N, Polder E, van Berkel C, et al. Defective glial maturation in vanishing white matter disease. J Neuropathol Exp Neurol 2011;70:69-82.