TUBB4A-related hypomyelinating leukodystrophy
General description
TUBB4A-related hypomyelinating leukodystrophy is a form of leukoencephalopathy resulting from mutations in the TUBB4A gene, which encodes β-tubulin. This protein forms heterodimers with α-tubulin, playing a critical role in microtubule formation essential for cytoskeletal integrity. The tubulin β-4A encoded by TUBB4A is brain-specific and exhibits high expression levels in the cerebellum, putamen, and white matter, particularly within oligodendrocytes.
Many cases show no abnormalities at birth. The onset varies from infancy to adulthood, with the severity of motor and intellectual disability, extrapyramidal symptoms (such as spastic paralysis), cerebellar symptoms (like ataxia), and bulb symptoms (including dysarthria and dysphagia) varying widely. Extrapyramidal symptoms are present in almost all cases.
Hypomyelination
-
CerebrumCerebral white matter
In TUBB4A-related hypomyelinating leukodystrophy, cerebral white matter displays diffuse hyperintensity on T2WI and FLAIR due to hypomyelination.
Striatal atrophy and aplasia
-
Putamen
-
Caudate nucleus
In TUBB4A-related hypomyelinating leukodystrophy, striatal atrophy is primarily observed in the putamen. As the disease progresses, atrophy extends to the caudate nuclei.
Atrophy
-
Cerebrum
-
Cerebellum
-
Corpus callosum
There is also atrophy of the cerebellum, particularly affecting the cerebellar vermis, in addition to observable atrophy in both the cerebral regions and the corpus callosum.
Corticospinal tract lesion
-
Corticospinal tract
The bilateral corticospinal tracts are also affected, showing T2WI and FLAIR hyperintensity.