Alexander’s disease was identified in 1949 on neuropathological criteria, that is, the presence of Rosenthal fibers and myelin loss.
Forms of the disease
The infantile form (from birth to 2 years) is the most frequent, it is characterized by an early onset and a severe course. Its symptomatology combines progressive megalencephaly (sometimes hydrocephalus), retarded psychomotor development or regression, pyramidal signs, ataxia and convulsive seizures. CT scan and MRI confirmthe diagnosis by showing white matter abnormalities with a predominance in the frontal areas.
The juvenile forms begin at school age and associate spastic paraplegia and progressive bulbar signs. Adult cases are heterogeneous and difficult to diagnose. This rare pathology, often considered as leukodystrophy, is usually sporadic; only a few family cases have been reported.
Genetics and diagnosis
The discovery of Rosenthal fibers in transgenic mice overexpressing the human GFAP (Glial Fibrillary Acidic Protein) protein, led to the search for mutations in the gene.
More than 20 mutations have been identified in the coding sequence of GFAP. These are dominant mutations that have arisen de novo. However, prenatal diagnosis seems desirable given the risk of germinal mosaicism.
Currently, treatment is only symptomatic.