Clinical and instrumental gait phenotyping in people with GLUT-1 deficiency syndrome

Abstract

Objectives: Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare neurometabolic disorder caused by mutations in the SLC2A1 gene. GLUT1-DS is characterized by epilepsy, cognitive impairment, movement disorders, and gait abnormalities. In the present study we aimed to characterize gait features of GLUT1-DS by means of gait analysis based on a single inertial measurement unit.

Methods: We conducted a case-control study with 32 GLUT1-DS patients (22.4 ± 13.2 years; 13 males) and 32 matched healthy participants (HS). Participants underwent inertial gait analysis, providing spatio-temporal and trunk acceleration-derived gait indexes, including harmonic ratio (HR), largest Lyapunov exponent (sLLE), log-dimensionless jerk score of accelerations (LDLJa), and step length variability (CV).

Results: Compared to HS, GLUT1-DS patients showed decreased HR (P < 0.005) across all directions, reflecting reduced symmetry and smoothness of trunk acceleration during gait. sLLE was higher in GLUT1-DS, indicating gait instability (P < 0.005), and LDLJa was elevated (P = 0.001), corroborating lower smoothness of trunk accelerations. Step length variability was also higher in GLUT1-DS patients (P = 0.001).

Interpretation: The gait pattern of GLUT1-DS patients is marked by reduced fluidity, stability, and smoothness. Inertial gait analysis could be a valuable tool for monitoring GLUT1-DS progression and tailoring rehabilitative strategies.

Keywords: GLUT1 deficiency syndrome; Gait child neurology; Ketogenic diet therapy; Ketones; Movement disorder.