Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC)
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Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare neurodegenerative hypomyelinating disease of infancy and childhood.
Due to the small number of reported cases, detailed epidemiological data is unavailable. The age of onset is usually within the first three years 2.
Children are usually normal at birth but then fail to thrive and develop wide-ranging neurological deficits including movement abnormalities (e.g. extrapyramidal signs, spasticity and ataxia), cognitive impairment, hypotonia, nystagmus, and sometimes seizures 2. A substantial minority of affected individuals are able to gain some mobility (e.g. walking without support), speech and feeding, only to gradually lose it over a number of years.
It appears that H-ABC results from de novo (i.e. noninherited) autosomal dominant mutations of TUBB4A, a gene that encodes tubulin β-4A 2. Tubulins polymerize to form microtubules, which are cardinal components of the cytoskeleton in eukaryotes.
The features of H-ABC are as the name suggests 1,2:
- hypomyelination of the cerebrum and large white matter tracts including:
- atrophy of the basal ganglia
- atrophy of the cerebellum
Treatment and prognosis
No treatment is available and given the small number of patients reported, accurate generalizations about prognosis are not available. The rate of decline and severity of neurological deficits is variable, with some individuals identified with H-ABC being as old as 29 years of age at the time of publication (c. 2014) 2. A significant number of individuals, however, die in childhood or early adulthood 2.
- 1. Mercimek-Mahmutoglu S, van der Knaap M, Baric I, Prayer D, Stoeckler-Ipsiroglu S. Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC). Report of a New Case. Neuropediatrics. 2005;36(3):223-6. doi:10.1055/s-2005-865715 - Pubmed
- 2. Hamilton E, Polder E, Vanderver A et al. Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum: Further Delineation of the Phenotype and Genotype-Phenotype Correlation. Brain. 2014;137(Pt 7):1921-30. doi:10.1093/brain/awu110 - Pubmed
- 3. Ferreira C, Poretti A, Cohen J, Hamosh A, Naidu S. Novel TUBB4A Mutations and Expansion of the Neuroimaging Phenotype of Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC). Am J Med Genet A. 2014;164A(7):1802-7. doi:10.1002/ajmg.a.36526 - Pubmed