Design of a Pediatric Low Motor Function Item Battery in leukodystrophies

Leukodystrophies are rare genetic disorders that disrupt myelin formation in the central nervous system, leading to a broad range of neuromotor impairment. Standard assessment tools, including the Gross Motor Function Measure-88 (GMFM-88), were designed to favor higher-level skills, like sitting and walking, with more limited sensitivity for earlier developmental skills. In populations where advanced gross motor skills can be profoundly limited, there is a critical need for sensitive clinical outcome assessments capable of detecting motor changes across the gross motor spectrum. This study describes the development and preliminary evaluation of the Pediatric Low Motor Function Item Battery (P-LoMo), designed to extend sensitivity into the lowest ranges of ability. Items were selected from validated assessments, including the Test of Infant Motor Performance, the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders, the Bayley Scales of Infant and Toddler Development-4th Edition, the Mullen Scales of Early Learning, and the Early Clinical Assessment of Balance, through expert consensus. The P-LoMo and the GMFM-88 were administered to 168 leukodystrophy patients. Median GMFM-88 performance was 17.5%, with a skew to low performance (52% of scores within the bottom 20%). The P-LoMo median score was 71 out of 84 potential points. There was a strong correlation between assessments (Spearman's R = 0.94, p < 0.0001) across the total cohort as well as among individuals in the lowest register of performance on the GMFM-88 (Spearman's R = 0.90, p < 0.0001). The P-LoMo has the potential to improve our capacity to capture the full range of neurologic function for children with leukodystrophies and severe motor impairment. It provides a sensitive, feasible, and caregiver-aligned clinical outcome assessment. This tool has the potential to improve trial readiness, functional quantification, and evaluation of emerging therapies in pediatric populations with low motor function.