Association between homozygous c.318A>GT mutation in exon 2 of the EIF2B5 gene and the infantile form of vanishing white matter leukoencephalopathy

Abstract

Background: Vanishing white matter disease is one of the most frequent leukodystrophies in childhood with autosomal recessive inheritance. A mutation in one of the genes encoding the five subunits of the eukaryotic translation initiation factor 2 (EIF2B5) is present in 90% of the cases. The diagnosis can be made by clinical and neuroradiological findings and molecular tests. Case report: We describe a thirteen-month-old male with previous normal neurodevelopment, who was hospitalized for vomiting, hyperthermia, and irritability. On examination, cephalic perimeter and cranial nerves were normal. Hypotonia, increased deep tendon reflexes, generalized white matter hypodensity on head tomography were found. Fifteen days after discharge, he suffered a minor head trauma presenting drowsiness and focal seizures. Magnetic resonance showed generalized white matter hypointensity. Vanishing white matter disease was suspected, and confirmed by sequencing of the EIF2B5 gene, revealing a homozygous c.318A> T mutation in exon 2. Subsequently, visual acuity was lost and cognitive, and motor deterioration was evident. The patient died at six years of age due to severe pneumonia. Conclusions: This case contributes to the knowledge of the mutational spectrum of VWM in Mexican patients and allows extension of the phenotype associated to this mutation.

Adult-Onset White Matter Vanishing Disease With Ovarian Failure in a Salvadoran Patient

“…They also described a sex prevalence ratio of 1:1.21 for males and females, with a female predominance in the adult-onset group [ 5 ]. Few infantile-onset cases have been reported in the Mesoamerican [ 6 , 7 ] and South American populations. Varying clinical features include spastic paraparesis, gait instability, cerebellar ataxia, tremors, weakness, psychiatric manifestations, and cognitive impairment.…”

EIF2B2 gene mutation causing early onset vanishing white matter disease: a case report

“…Although refractory generalized tonic- myoclonic seizures were previously described [ 23 , 24 , 27 ], clinical presentation of epilepsy is poorly documented and do not include detailed information about the type, time of onset and severity of seizures. Most of patients reported in Table 1 present conditions of stress as a trigger of rapid and major neurological worsening [ 18 , 20 , 21 , 23 , 25 ].…”