Glial Protein Mutations in Alexander Disease

The role of glial fibrillary acidic protein (GFAP) mutations in Alexander disease was analyzed in 44 patients, including 18 with later onset, at the University of Alabama, Birmingham, AL, and at other centers in the US, UK and Europe. Missense mutations had been identified previously (Brenner M et al, 2001) in the GFAP gene in 11 of 12 infantile Alexander disease patients. Based on age at onset, patients were classified as infantile (<2 years old, 26 patients), juvenile (2-12 yrs, 15 pts), or adult (>13 yrs, 3 pts). Age at onset ranged from birth to 1.5 yrs for infantile, and from 2 to 11.5 yrs for juvenile. Clinical presentation of infantile cases included seizures (92%) and failure to meet milestones of development, with macrocephaly (62%), spasticity (52%), bulbar signs (62%), ataxia (58%), and cognitive defects (82%). Diagnosis was confirmed by pathology (Rosenthal fibers) or MRI. Dominant missense GFAP mutations were found in all forms of Alexander disease, with male predominance in the juvenile variety. [1]