Adult-Onset Vanishing White Matter Disease Due to a Novel EIF2B3 Mutation

Abstract

To report a novel mutation in the gene EIF2B3 responsible for a late-onset form of vanishing white matter disease.

Brain magnetic resonance imaging helps to differentiate atypical multiple sclerosis with cavitary lesions and vanishing white matter disease

“…The morphology of the lesions, specifically those previously described to be suggestive of MS [ovoid and perpendicular lesions to the lateral ventricles (Dawson's fingers type), isolated juxtacortical lesions in the U-fibres), was also analysed [7]. Additionally, the following lesions previously found in VWMD were analysed [5,8]: extensive corpus callosum involvement, extensive involvement of the external capsule, bilateral and symmetrical posterior fossa involvement. The topography of the cavitary lesions was analysed with respect to the presence of an anterior predominance of the lesions.…”

Advances In the Diagnosis of Leukodystrophies

“…Various etiologies have been described as causing myelination delay, such as chromosomal abnormalities (e.g., trisomy 21), inborn errors of metabolism (e.g., methylmalonic acidemia [20] and phenylketonuria [21]) and acquired causes (e.g., hypoxic-ischemic encephalopathy [22]). One exception to this is the X-linked disorder, Allan-Herndon-Dudley syndrome, formerly called MCT8-specific thyroid hormone cell transporter deficiency, a disorder characterized by myelination delay, but that presents [58,71,73,82] Endocrine Adrenal insufficiency Adrenoleukodystrophy [5] Ovarian dysfunction Vanishing white matter disease [36] Hypogonadotropic hypogonadism (delayed puberty)…”

“…AR AD HEPACAM Molecular (clinical) [39] Metachromatic AR ARSA ARSA enzymatic activity (leukocytes, fibroblasts) with urine sulfatides † Molecular (clinical) [4] Metachromatic-like (normal ARSA enzymatic activity) due to saposin B deficiency AR PSAP Urine sulfatides Saposin B levels Molecular (clinical) [87] Austin variant of metachromatic leukodystrophy caused by multiple sulfatase deficiency AR SUMF1 Urine sulfatides, urine MPS, ARSA enzymatic activity Molecular (clinical) [88] Vanishing white matter disease AR EIF2B1-5 Molecular (clinical) [36,38] [36,37], including the disorder formerly called 'ovarioleukodystrophy' [37] characterized by the presence of premature menopause due to ovarian failure. Some adult cases have also been reported with a classic history of complicated migraines preceding the neurological deterioration [36,38].…”

“…Some adult cases have also been reported with a classic history of complicated migraines preceding the neurological deterioration [36,38]. The brain MRI reveals a demyelinating leukodystrophy with characteristic white matter rarefaction [13].…”

Functional implications of demyelination and the molecular control of remyelination in the adult mouse.

“…However, late onset has been documented late into adulthood and is commonly misdiagnosed as schizophrenia due to white matter lossinduced psychosis (Matsukawa et al, 2011;La Piana et al, 2012).…”