Abstract
Treatment outcomes from pallidal deep brain stimulation are highly heterogeneous reflecting the phenotypic and etiologic spectrum of dystonia. Treatment stratification to neurostimulation therapy primarily relies on the phenotypic motor presentation; however, etiology including genetic factors are increasingly recognized as modifiers of treatment outcomes. Here, we describe a 53 year-old female patient with a progressive generalized dystonia since age 25. The patient underwent deep brain stimulation of the globus pallidus internus (GPi-DBS) at age 44. Since the clinical phenotype included mobile choreo-dystonic features, we expected favorable therapeutic outcome from GPi-DBS. Although mobile dystonia components were slightly improved in the long-term outcome from GPi-DBS the overall therapeutic response 9 years from implantation was limited when comparing “stimulation off” and “stimulation on” despite of proper electrode localization and sufficient stimulation programming. In order to further understand the reason for this limited motor symptom response, we aimed to clarify the etiology of generalized dystonia in this patient. Genetic testing identified a novel heterozygous pathogenic SLC2A1 mutation as cause of glucose transporter type 1 deficiency syndrome (GLUT1-DS). This case report presents the first outcome of GPi-DBS in a patient with GLUT1-DS, and suggests that genotype relations may increasingly complement phenotype-based therapy stratification of GPi-DBS in dystonia.
Highlights
GLUT1-DS (OMIM #606777) arises from impaired glucose transport into the brain because of SLC2A1 mutations
We consider the novel heterozygous SLC2A1 variant (c.972 + 1delG) as pathogenic mutation, since both clinical features and disease course are consistent with previously described phenotypes of GLUT1-DS
Molecular genetic panel testing including the SLC2A1 gene was initiated with temporal delay from GPi-DBS owing to dystonia panel analysis
Summary
GLUT1-DS (OMIM #606777) arises from impaired glucose transport into the brain because of SLC2A1 mutations. The syndrome was first described in 1991 [6], and may present considerable phenotypic variability potentially including infantile seizures, developmental delay, cognitive impairment, microcephaly and various movement disorders [7]. Most common movement disorders include dystonia, chorea and myoclonus [8] as well as exercise-induced dyskinesias [9]. Clinical variability depends on the type of mutation in SLC2A1 gene [10]. Ketogenic diet and modified Atkins diet show variable efficacy on clinical symptoms [11, 12]. Sensors comprising tri-axial accelerometer, gyroscope, and magnetometer were attached to both ankles lumbar position (Opal, APMD Inc, Portland, OR, USA). Kinematic gait measures were computed with Mobility Lab (APMD Inc, Portland, OR, USA) [4]
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