Objective: To highlight the presentation of TUBB4A mutations.

Background: Hypomyelinating leukodystrophy, identified in 2002 by magnetic resonance imaging is a rare heterogeneous group of diseases that is recognized in infancy and child hood, it is characterized by extrapyramidal movements, spasticity, cognitive deficits, cerebellar ataxia and epilepsy. It is caused by mutations in TUBB4A, which can range from type 4 dystonia (DYT4) or hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC).

Methods: We report 2 sibblings with de novo mutations in TUBB4A gene.

Results: Both sibblings developed progressive difficulties in ambulation and balance with significant cognitive impairment and variable abnormal movements. Neuroimaging showed hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum. All other investigations were normal. Extended WES analysis revealed the heterozygous missence mutation c.745G>A (p.Asp249Asn) in Exon 4 of the TUBB4A gene.

Conclusions: Hypomyelinating leukodystrophies poses a diagnostic challenge. TUBB4A mutation should be considered in all cases of isolated hypomyelination with or without cerebellar and basal ganglia atrophy due to its variable clinical presentations lacking the typical clinical features. A trial of L-dopa as a possible symptomatic treatment should be considered.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/whole-exome-sequencing-wes-identifies-a-tubb4a-mutation-in-two-saudi-siblings-with-hypomyelinating-leukodystrophy-associated-with-atrophy-of-basal-ganglia-and-cerebellum/