Familial paroxysmal exercise-induced dyskinesia and benign epilepsy: a clinical and neurophysiological study of an uncommon disorder

Margari, Lucia; Perniola, T; Illiceto, G.; Ferrannini, E.; Iaco, M.G. De; Presicci, Anna; Santostasi, R.; Ventura, Paolo

doi:10.1007/s100720070092

Cited by 35 publications

(16 citation statements)

References 22 publications

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“…Our patients presented with PED episodes anteceding in several years the presentation of absence seizures as reported previously in familial PED [16]. PED, at least regarding sporadic cases, appears to be a genetically heterogeneous disorder [13]; it is reasonable to postulate that co-occurrence of absence seizures may represent a clinical signature of GLUT1DS-related PED.…”

Section: Discussionmentioning

confidence: 72%

Paroxysmal exercise-induced dyskinesia, writer's cramp, migraine with aura and absence epilepsy in twin brothers with a novel SLC2A1 missense mutation

Urbizu

Cuenca-León

Raspall-Chaure

et al. 2010

Journal of the Neurological Sciences

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Section: Discussionmentioning

confidence: 72%

Paroxysmal exercise-induced dyskinesia, writer's cramp, migraine with aura and absence epilepsy in twin brothers with a novel SLC2A1 missense mutation

Urbizu

Cuenca-León

Raspall-Chaure

et al. 2010

Journal of the Neurological Sciences

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“…All procedures were in accordance with the Helsinki Convention and were approved by the Ethical Committees of the University of Ulm, the University of Tübingen, the University of Bari, the National Hospital for Neurology and Neurosurgery, and the Institute of Neurology Joint Research. The clinical features of families PED2-4 have been described previously (24)(25)(26).…”

Section: Methodsmentioning

confidence: 99%

GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak

Weber¹,

Storch²,

Wuttke³

et al. 2008

J. Clin. Invest.

335

275

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Paroxysmal dyskinesias are episodic movement disorders that can be inherited or are sporadic in nature. The pathophysiology underlying these disorders remains largely unknown but may involve disrupted ion homeostasis due to defects in cell-surface channels or nutrient transporters. In this study, we describe a family with paroxysmal exertion-induced dyskinesia (PED) over 3 generations. Their PED was accompanied by epilepsy, mild developmental delay, reduced CSF glucose levels, hemolytic anemia with echinocytosis, and altered erythrocyte ion concentrations. Using a candidate gene approach, we identified a causative deletion of 4 highly conserved amino acids (Q282_S285del) in the pore region of the glucose transporter 1 (GLUT1). Functional studies in Xenopus oocytes and human erythrocytes revealed that this mutation decreased glucose transport and caused a cation leak that alters intracellular concentrations of sodium, potassium, and calcium. We screened 4 additional families, in which PED is combined with epilepsy, developmental delay, or migraine, but not with hemolysis or echinocytosis, and identified 2 additional GLUT1 mutations (A275T, G314S) that decreased glucose transport but did not affect cation permeability. Combining these data with brain imaging studies, we propose that the dyskinesias result from an exertion-induced energy deficit that may cause episodic dysfunction of the basal ganglia, and that the hemolysis with echinocytosis may result from alterations in intracellular electrolytes caused by a cation leak through mutant GLUT1.

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“…Interestingly, tremor was the only permanent symptom in 2 of these 12 patients (same family) between episodes of PED and headache (Münchau et al 2000). This suggests that tremor may be the sole symptom of GLUT1-DS, in keeping with the incomplete penetrance of this syndrome (Weber et al 2008;Suls et al 2008Suls et al , 2009Mullen et al 2010;Margari et al 2000;Leen et al 2010). However, in most cases (12/14), the tremor is associated with other permanent, mostly mild, neurological disorders, and often with a family history of tremor (6/14).…”

Section: Discussionmentioning

confidence: 94%

Dystonic tremor caused by mutation of the glucose transporter gene GLUT1

Roubergue

Apartis

Mesnage

et al. 2011

J of Inher Metab Disea

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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.

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Familial paroxysmal exercise-induced dyskinesia and benign epilepsy: a clinical and neurophysiological study of an uncommon disorder

Cited by 35 publications

References 22 publications

Paroxysmal exercise-induced dyskinesia, writer's cramp, migraine with aura and absence epilepsy in twin brothers with a novel SLC2A1 missense mutation

Paroxysmal exercise-induced dyskinesia, writer's cramp, migraine with aura and absence epilepsy in twin brothers with a novel SLC2A1 missense mutation

GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak

Dystonic tremor caused by mutation of the glucose transporter gene GLUT1

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