Since genetic analysis of the GFAP gene for the diagnosis of adult Alexander disease (AD) has been established in 2001, several cases of both sporadic and familial cases of AD have been described. Except for one patient, all subjects revealed glial fibrillary acidic protein (GFAP) mutations, and clinical progression of symptoms, mainly bulbar and pseudobulbar, were moderate. Here we report on a patient with acute onset of vegetative symptoms, rapid progression, and death within 2 months. Although histology and final magnetic resonance imaging (MRI) were characteristic of AD, sequencing of the encoding GFAP gene revealed no mutation. We believe that this case report expands the so far known clinical spectrum and MRI dynamics of adult AD, and suggest that analysis of the coding part of GFAP may be inconclusive in rare cases. In such patients, only histology may lead to definitive diagnosis.