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.

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 .

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 . 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. not inherited) autosomal dominant mutations of TUBB4A, a gene which encodes tubulin β-4A .

Radiographic features

MRI

The features of H-ABC are as the name suggests :

  • 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 putamen
    • normal-sized thalamus and globus pallidus
    • variable atrophy of caudate nucleus
  • 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 reporting . A significant number of individuals, however, die in childhood or early adulthood .

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 .