Dystonic tremor caused by mutation of the glucose transporter gene GLUT1

Abstract

Glucose transporter 1 deficiency syndrome (GLUT1-DS) is due to heterozygous mutation of the glucose transporter type 1 gene (GLUT1/SLC2A1). GLUT1-DS is characterized by movement disorders, including paroxysmal exercise-induced dystonia (PED), as well as seizures, mental retardation and hypoglycorrhachia. Tremor was recently shown to be part of the phenotype, but its clinical and electrophysiological features have not yet been described in detail, and GLUT1 tremor reports are rare. We describe two patients, a young woman and her mother, who were referred to us for tremor. We also systematically review published cases of GLUT1-DS with tremor (14 cases, including ours), focusing on clinical features. In most cases (10/14), the tremor, which involved the limbs and voice, fulfilled clinical criteria for dystonic tremor (DT), occurring in body areas affected by dystonia. Tremor was the only permanent symptom in 2 cases. Recordings, reported here for the first time, showed an irregular 6- to 8.5-Hz tremor compatible with DT in our two patients. These findings show that tremor, and particularly DT, may be a presenting symptom of GLUT1-DS. Patients who present with dystonic tremor, with or without mental retardation, seizures, movement disorders and/or a family history, should therefore be screened for GLUT1-DS.

Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites

“…Mutations were identified in this and 3 other PED families 231. Mutations in SLC2A1 have also been found in sporadic cases of PED232 and in a family with dystonic tremor as the presenting feature 233. SLC2A1/GLUT1 is the main glucose transporter in the brain.…”

Nationwide survey of glucose transporter-1 deficiency syndrome (GLUT-1DS) in Japan

“…Although patients with missense mutations often exhibit mild symptoms (especially mental retardation), a clear genotype-phenotype relationship has not yet been established. SLC2A1 gene mutations have also recently been identified in some patients with paroxysmal exercise-induced dyskinesia, early-onset absence epilepsy, and myoclonic-astatic epilepsy, and GLUT-1DS is now considered to have a wide spectrum of phenotypes [3,[10][11][12][13][14][15][16]. Approximately 200 cases of GLUT-1DS have been reported to date, mainly in the US and Europe [17].…”

Update on dystonia

“…The DYT21 locus was recently mapped in a family from Northern Sweden, whose phenotype was characterized by adult onset in the cranial-cervical muscles or in the hands and progression to generalization or multifocal distribution [16]. Mutations in SLC2A1 have also been found in sporadic cases [20] and in a family with dystonic tremor as the presenting feature [21]. Their phenotype differs from the typical dystonia presentation due to the addition of chorea and other hyperkinetic features [17 & ].…”