GLUT1 gene mutations cause sporadic paroxysmal exercise-induced dyskinesias

Abstract

Paroxysmal exercise-induced dyskinesias (PED) are involuntary intermittent movements triggered by prolonged physical exertion. Autosomal dominant inheritance may occur. Recently, mutations in the glucose transporter 1 (GLUT1) gene (chr. 1p35-p31.3) have been identified as a cause in some patients with autosomal dominant PED. Mutations in this gene have previously been associated with the GLUT1 deficiency syndrome. We performed mutational analysis in 10 patients with apparently sporadic PED. We identified two novel GLUT1 mutations, at least one likely to be de-novo, in two of our patients. Onset was in early childhood. One of our patients had a predating history of childhood absence epilepsy and a current history of hemiplegic migraine as well as a family history of migraine. The other patient had no other symptoms apart from PED. Brain MRI showed cerebellar atrophy in one case. Mutations in GLUT1 are one cause of apparently sporadic PED. The detection of this has important implications for treatment as ketogenic diet has been reported to be beneficial.