Objective: To identify Clinical Outcome Assessments (COAs) appropriate for the evaluation of paroxysmal movement disorder symptoms and functional impact in Glut1 DS.

Background: Glut1 DS is a rare, genetic disorder characterized by impaired glucose transport to the brain, causing cerebral energy deficiencies. Symptoms can include seizures, movement disorders and cognitive impairment. Movement disorders associated with Glut1 DS can be continuous or paroxysmal with variable presentation. Patient and clinician reported measures and performance based tests were evaluated for their relevance and to inform endpoint selection for clinical trials.

Methods: Patients with a confirmed Glut1 DS diagnosis and a history of movement disorder symptoms attended a 1-day visit. Assessments included caregiver/patient interviews and questionnaires (SF-10/SF-12), tests of walking capacity (12MWT) and fine and gross motor function (BOT-2), and clinician-rated scales of ataxia and abnormal dyskinesias. Actigraphy, using a wrist worn device, was assessed for ≤10 days after the visit.

Results: Seven patients (5 pediatric/2 adults) participated in the study. Patients/caregivers reported impaired physical health secondary to movement disorder symptoms with a mean SF-10 Physical Summary Score ~3SD below normative values. Participants reported some difficulties with activities of daily living (ADLs) due to continuous symptoms, with increased difficulty or inability to perform ADLs during a paroxysmal event. All subjects had impaired walking capacity as demonstrated by a mean 6-minute walk distance of 69% predicted during the 12MWT. Fine and gross motor function were not consistently impaired based on BOT-2 scores. Clinician-rated scales showed a minimal level of ataxia and abnormal movements at the time of testing. None of the subjects experienced a paroxysmal movement disorder event during testing. Actigraphy analysis suggests significantly less daytime activity compared to controls.

Conclusions: Glut1 DS paroxysmal movement disorder events substantially affect physical function and ability to perform ADLs. The assessments studied were sensitive to the functional limitations of the subjects. However, as no paroxysmal events were observed during the visit, use of a daily diary may be more appropriate to capture the impact of these unpredictable and disabling events.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/assessments-of-movement-disorder-symptoms-and-functional-impacts-in-glucose-transporter-type-1-deficiency-syndrome-glut1-ds/