Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare neurodegenerative hypomyelinating disease of infancy and childhood.
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Epidemiology
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.
Clinical presentation
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.
Pathology
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.
Radiographic features
MRI
The features of H-ABC are as the name suggests 1,2:
- hypomyelination of the cerebrum and large white matter tracts including:
- hypoplasia of the corpus callosum
- involvement of the pyramidal tracts through the internal capsule
- atrophy of the basal ganglia
- marked atrophy of the putamina
- normal-sized thalami and globi pallidi
- variable atrophy of caudate nuclei
- 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.
Differential diagnosis
The differential diagnosis is broadly that of other leukodystrophies that present in infancy, but more particularly other disorders of hypomyelination such as Pelizaeus-Merzbacher disease 1.