Leukodystrophy, Hypomyelinating, 6 (HLD6)

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OMIM®: ⁵⁷ Hypomyelinating leukodystrophy-6, also known as hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum, is a neurologic disorder characterized by onset in infancy or early childhood of delayed motor development and gait instability, followed by extrapyramidal movement disorders, such as dystonia, choreoathetosis, rigidity, opisthotonus, and oculogyric crises, progressive spastic tetraplegia, ataxia, and, more rarely, seizures. Most patients have cognitive decline and speech delay, but some can function normally. Brain MRI shows a combination of hypomyelination, cerebellar atrophy, and atrophy or disappearance of the putamen. The disorder usually shows sporadic occurrence, but sibs may be affected if a parent is somatic mosaic for the mutation (summary by Simons et al., 2013). Hypomyelinating leukodystrophies (HLD) comprise a genetically heterogeneous entity in which there is a substantial permanent deficit in myelin deposition within the brain, resulting in neurologic deficits (van der Knaap et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080. (612438) (Updated 08-Dec-2022)

MalaCards based summary: Leukodystrophy, Hypomyelinating, 6, also known as hypomyelinating leukodystrophy 6, is related to leukodystrophy, hypomyelinating, 3 and leukodystrophy, hypomyelinating, 11, and has symptoms including ataxia, tremor and seizures. An important gene associated with Leukodystrophy, Hypomyelinating, 6 is TUBB4A (Tubulin Beta 4A Class IVa), and among its related pathways/superpathways are Cell Cycle, Mitotic and Vesicle-mediated transport. Affiliated tissues include cerebellum, brain and eye, and related phenotypes are nystagmus and hearing impairment

GARD: ¹⁹ Hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC) is a disease that affects certain parts of the brain. Symptoms may include delayed motor development, learning difficulties, upper-motor neuron dysfunction (spasticity, exaggerated reflexes, and Babinski signs), dystonia, rigidity, involuntary movements, and speech and swallowing problems. H-ABC is caused by a genetic change in the TUBB4A gene. Inheritance is autosomal dominant, but most cases are due to a new genetic change occurring for the first time in a person with the condition.

UniProtKB/Swiss-Prot: ⁷³ A neurologic disorder characterized by onset in infancy or early childhood of delayed motor development and gait instability, followed by extrapyramidal movement disorders, such as dystonia, choreoathetosis, rigidity, opisthotonus, and oculogyric crises, progressive spastic tetraplegia, ataxia, and, more rarely, seizures. Most patients have cognitive decline and speech delay, but some can function normally. Brain MRI shows a combination of hypomyelination, cerebellar atrophy, and atrophy or disappearance of the putamen.

Disease Ontology: ¹¹ A hypomyelinating leukodystrophy characterized by infant or early childhood onset of delayed motor development and gait instability, followed by extrapyramidal movement disorders, progressive spastic tetraplegia, ataxia, hypomyelination, cerebellar atrophy, and atrophy or disappearance of the putamen that has material basis in heterozygous mutation in the TUBB4A gene on chromosome 19p13.

Orphanet: ⁵⁸ A rare disorder characterized by slowly progressive spasticity, extrapyramidal movement disorders (dystonia, choreoathetosis and rigidity), cerebellar ataxia, moderate to severe cognitive deficit, and anarthria/dysarthria.

Clinical features from OMIM®:

Search Clinical Trials, NIH Clinical Center for Leukodystrophy, Hypomyelinating, 6