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

Published online by Cambridge University Press:  25 October 2024

Sangeeth Thuppanattumadam Ananthasubramanian ,
Gautham Arunachal ,
Hansashree Padmanabha  and
Rohan Ramachandra Mahale Open the ORCID record for Rohan Ramachandra Mahale [Opens in a new window]
Sangeeth Thuppanattumadam Ananthasubramanian
Affiliation:
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, KA, India
Gautham Arunachal
Affiliation:
Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bengaluru, KA, India
Hansashree Padmanabha
Affiliation:
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, KA, India
Rohan Ramachandra Mahale*
Affiliation:
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, KA, India
*
Corresponding author: Rohan Ramachandra Mahale; Email: [email protected]
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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.

Résumé :

RÉSUMÉ :

Pathologies du gène EIF2B chez l’adulte : profil clinique, d’imagerie et génétique avec une revue de la littérature.

Contexte :

Le syndrome de disparition de la matière blanche (DMB) est l’une des leuco-encéphalopathies causées par des mutations récessives du gène EIF2B1-5. Les pathologies du gène EIF2B chez l’adulte (apparition clinique après l’âge de 16 ans) ont été signalées comme étant moins fréquentes.

Objectif :

Décrire le profil clinique, génétique et d’imagerie des pathologies du gène EIF2B de l’adulte et comparer une cohorte de patients indiens avec des cohortes de patients asiatiques et européens.

Méthodes :

Se pencher sur deux cas de pathologies du gène EIF2B apparus à l’âge adulte ; passer en revue de façon complète les pathologies du gène EIF2B apparues à l’âge adulte et confirmées génétiquement depuis 2001 dans des cohortes de patients indiens, asiatiques et européens.

Résultats :

À noter que 2 patients étaient des femmes dont l’âge médian, au moment de la présentation, était de 25,5 ans (24-27) et de 19 ans (18-20) lors de l’apparition des premiers symptômes de la maladie. La durée médiane des symptômes était de 6,5 ans (6-7). Toutes deux donnaient à voir une ataxie cérébelleuse, une spasticité, des troubles cognitifs et une atteinte de la vessie. Un examen d’IRM du cerveau a montré une leuco-encéphalopathie avec raréfaction chez ces deux patientes ainsi qu’une atteinte du corps calleux chez une d’entre elles. Un test génétique a aussi révélé une variante homozygote faux-sens du gène EIF2B3 chez ces deux femmes. La cohorte indienne de 7 patients présentait quant à elle des caractéristiques cliniques et radiologiques similaires et des variantes communes du gène EIF2B3 (n = 4). La cohorte asiatique, elle, comptait 24 cas tandis que la cohorte européenne comptait 61 cas avec des caractéristiques cliniques et radiologiques similaires et des variantes communes dans le gène EIF2B5.

Conclusion :

Les pathologies du gène EIF2B chez l’adulte révèlent un profil clinique distinct ainsi qu’une prédominance féminine. À titre de manifestations cliniques les plus courantes, cela se traduit notamment par l’ataxie cérébelleuse, la spasticité et un déclin cognitif. Ajoutons également la leuco-encéphalopathie avec raréfaction observée lors d’examens d’IRM. Les variantes du gène EIF2B5 sont fréquentes au sein des cohortes de patients asiatiques et européens tandis que celles du gène EIF2B3 le sont dans la cohorte de patients indiens.

Keywords

Adult-onsetEIF2Bleukoencephalopathyvanishing white matter
Type
Original Article
Information
Canadian Journal of Neurological Sciences , First View , pp. 1 - 8
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation

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