Familial acanthocytosis with paroxysmal exertion-induced dyskinesias and epilepsy (FAPED)
Neuroacanthocytoses are inherited disorders with abnormal erythrocytes and neurological symptoms. Paroxysmal dyskinesias are characterized by attacks of involuntary movements classified as kinesiogenic, non-kinesiogenic or exertion-induced. We describe a novel dominant disease in a three-generation family with four affected individuals presenting with acanthocytosis, paroxysmal exertion-induced dyskinesias and epilepsy. The syndrome was characterized by extensive clinical work-up, neuroimaging, testing of erythrocytes and fibroblasts and genetic studies.
The 33-year-old index patient and his mother complained about attacks of cramps and involuntary movements after heavy workload since early childhood. Interictal neurologic examination was normal. Symptoms were relieved upon a ketogenic diet whereas response to carboanhydrase inhibitors was moderate. The nine-year-old son is little mentally retarded and suffers from mild permanent motor problems and focal epilepsy with myoclonic and atonic seizures occurring as status epilepticus in fasting state responding to ketogenic diet. The development of the two-year-old son was normal up to now. A mutation analysis of the Chorein gene, CHAC, was negative. Magnetic resonance imaging showed mild degenerative alterations within the basal ganglia and 18[F]-deoxy-glucose positron emission tomography a decreased glucose metabolism in the thalamus. Affected individuals presented with decreased CSF glucose, moderate hemolytic anemia and increased percentage of acanthocytes. Erythrocytes had a four-fold increased intracellular Na+ and a decreased K+ concentration. Membrane protein electrophoresis of erythrocytes, glucose uptake into fibroblasts, sequencing of the gene encoding the GLUT-1 glucose transporter and other electrophysiological and laboratory investigations were normal.