Adult-Onset EIF2B-Pathies: A Clinical, Imaging and Genetic Profiling with Literature Review.

Abstract

Background: Vanishing white matter syndrome is one of the leukoencephalopathies caused by recessive mutations in gene EIF2B1-5. Adult-onset EIF2B-pathies (clinical onset after age 16 years) have been reported to be less common.

Objective: Description of the clinical, imaging and genetic profile of adult-onset EIF2B-pathies and comparison of Indian cohort with Asian and European cohorts.

Methods: Report of two cases of adult-onset EIF2B-pathies and a comprehensive review of genetically confirmed adult-onset EIF2B-pathies since 2001 from Indian, Asian and European cohorts.

Results: Two patients were females, with median age at presentation of 25.5 years (24-27 years) and onset at 19 years (18-20 years). The median duration of symptoms was 6.5 years (6-7 years). Both had cerebellar ataxia, spasticity, cognitive impairment and bladder involvement. Brain magnetic resonance imaging (MRI) showed leukoencephalopathy with rarefaction in both patients and corpus callosum involvement in one patient. Genetics showed homozygous missense variant in the EIF2B3 gene in both patients. The Indian cohort of seven patients had similar clinical and radiological features and common variants in EIF2B3 (n = 4). The Asian cohort had 24 cases, and the European cohort had 61 cases with similar clinical features, radiological features and common variants in EIF2B5.

Conclusion: Adult-onset EIF2B-pathies have a distinct clinical profile of female predominance with cerebellar ataxia, spasticity and cognitive decline as the commonest triad of clinical manifestations and leukoencephalopathy with rarefaction on brain MRI. Variants in EIF2B5 were common in the Asian and European cohorts and EIF2B3 in the Indian cohort.