Rare Diseases Symptoms Automatic Extraction

Leukodystrophies with astrocytic dysfunction.

[alexander disease]

Astrocytic dysfunctions have been recently identified in four leukosdystrophies without peripheral nervous system myelin involvement. Alexander disease, the first primary genetic astrocytic disorder identified, is due to dominant GFAP mutations. The presence of Rosenthal fibers throughout the CNS is the pathological hallmark of this disease. Neurological degradation, megalencephaly, and typical MRI pattern are characteristic of infantile sporadic patients. Nevertheless, clinical and MRI expression is large, including late onset forms which can be familial. Spongiform or cystic white matter CNS degeneration is present in the other three recessive disorders. The visualization of a white matter cystic breakdown on MRI has led to the identification of CACH/VWM and MLC diseases. CACH/VWM is due to mutations in one of the five subunits of EIF2B which compromise the astrocytic lineage. The clinical spectrum is large, from antenatal to adult forms, and several extraneurological organs can be affected. Mutations in MLC1, which is mainly expressed in astrocyte endfeet, produce megalencephaly, whereas the mild clinical course contrasts with severe MRI features. An increased concentration of NAA in the urine is sufficient to diagnose Canavan disease, which is due to mutations of the ASPA gene. These disorders highlight the role of astrocytes in myelination or myelin maintenance.