Table of Contents
Washington University Experience | MYELIN (NON-IMMUNE MEDIATED) | Alexander Disease | 6A0 Case 6 History
Case 6 History Adult Alexander's disease with autosomal dominant transmission (AANP Diagnostic Slide Session, 2003, case 4) ---- This 67 year old woman presented a ten-year history of transient episodes of hypersomnolence, dysarthria, ataxia, psychomotor slowing and documented hypothermia (32°C). These episodes were self-resolving. In addition, the patient had long standing constipation and severe sleep apnea. A complete metabolic work-up including analyses of cerebrospinal fluid was negative. Magnetic resonance imaging revealed marked atrophy of the brainstem. An EEG revealed the presence of frontal epileptic spikes; however the patient never had any clinical manifestations of epilepsy. Frontal deficits were evident on neuropsychological testing. Several first-degree relatives of the patients were similarly affected. All shared with the patient a particular morphotype with marked kyphosis, arched palate and low hairline. The syndrome gradually progressed with dysphagia and dysarthria becoming increasingly severe. As well, cerebellar and pyramidal signs became more prominent. The patient ultimately died following complications of myocardial infarction at age 67. The brain weighed 1380 grams. Genetic testing of the patient's family has revealed a novel mutation in the first exon of the GFAP gene, in the rod domain of the protein. Five out of six heterozygotes in the family are symptomatic, with autosomal dominant transmission. (AANP Diagnostic Slide Session, 2003, case 4; also reported (Arch Neurol 2003, 60:1307-1312). Patients with chronic disease may show marked brainstem atrophy as in this case.
