Table 3. Leukodystrophies caused by a primary astrocyte defect.
Leukodystrophy | Gene defect | Astrocyte-mediated pathological mechanisms | Clinical and histopathological featuresshared among cystic leukodystrophies |
---|---|---|---|
Alexander’s disease (AxD) | Mutations in the glial fibrillary acidicprotein (GFAP) gene (130) | Accumulation of Rosenthal fibers, abnormal GFAP polimerization, defects in proteasomal degradation and authophagy processes, decrease in glutamate trasporters | Macrocephaly, ataxia, spasticity, epilepsy, aggravation of clinical conditions after minor head trauma and infections; limited genotype-phenotype correlation. Swollen white matter, astrocyte vacuolation |
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) | Mutations in the MLC1 or HEPACAM gene (168,178) |
Altered regulation of ion and fluid homeostasis and cell volume | Macrocephaly, ataxia, spasticity, mild cognitive decline, severe motor dysfunctions, epilepsy, subcortical cysts, aggravation of clinical conditions after minor head trauma. No genotype-phenotype correlation. Swollen white matter, astrocyte vacuolation |
Vanishing white matter syndrome (VWM) or childhood ataxia with central nervous system hypomyelination (CACH) | Mutations in the Eukariotic Translation Initiation Factor 2 (EIF-2B) gene (187) | Astrocyte maturation defect, abnormal response to stress conditions | Ataxia, spasticity, loss of vision, severe motor dysfunctions, mild cognitive decline, epilepsy, aggravation of clinical symptoms after minor stress conditions. Limited genotype-phenotype correlation. Swollen white matter |