Session Information
Date: Tuesday, September 24, 2019
Session Title: Pediatric Movement Disorders
Session Time: 1:45pm-3:15pm
Location: Agora 2 West, Level 2
Objective: This case report expand the phenotype of hypomyelination with atrophy of the basal ganglia and cerebellum.
Background: Background: Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare leukoencephalopathy associated with pathogenic mutations in TUBB4A, which encodes brain-specific tubulin-beta4A protein that is involved in the organization of microtubules. Patients present with extrapyramidal movements, spasticity, ataxia and cognitive deficits with those most severity affected presenting in infancy. The MRI features previously described are hypomyelination, progressive atrophy of the putamen and variable degrees of cerebellar atrophy. Iron accumulation in the basal ganglia has not been previously reported.
Method: Case summary: This boy initially presented at the age of 9 months with motor delay and was subsequently diagnosed with cerebral palsy at 13 months of age. The MRI brain at that time showed delayed myelination with cerebellar atrophy. Over the next few years, he developed spasticity in all four extremities, cogwheel rigidity in the upper extremities, axial hypotonia, generalized dystonia, facial bradykinesia, dysarthria, dysphagia, dysphonia, and significant drooling and had intellectual disability. A repeat MRI at 7 years of age showed marked delay in myelination with hypointense basal ganglia, apparent iron deposition in the Globus pallidi and hypoplastic cerebellum. He was tested for known genes associated with Neurodegeneration with brain iron accumulation (NBIA) that did not reveal any variants.
Results: Results: A dystonia gene panel (Invitae) identified a pathogenic heterozygous missense variant in TUBB4A, c.763G>A (p.Val255ile) in this autosomal dominant condition.
Conclusion: Conclusions: This report expands the radiological findings in TUBB4A mutations and highlights the importance of considering this gene in the evaluation of patients with brain iron accumulation.
To cite this abstract in AMA style:
C. Gorodetsky, I. Tein. TUBB4A mutation: Expansion of H-ABC phenotype with apparent iron accumulation in the basal ganglia – case report and literature review [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/tubb4a-mutation-expansion-of-h-abc-phenotype-with-apparent-iron-accumulation-in-the-basal-ganglia-case-report-and-literature-review/. Accessed August 15, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/tubb4a-mutation-expansion-of-h-abc-phenotype-with-apparent-iron-accumulation-in-the-basal-ganglia-case-report-and-literature-review/