Prospective 5-year natural history study of infantile PLA2G6-associated neurodegeneration

Area of Science:

• Neuroscience
• Genetics
• Pediatrics

Background:

• Infantile PLA2G6-associated neurodegeneration (PLAN) is a rare, progressive neurodegenerative disorder.
• Understanding the natural history of developmental milestones and quality of life is crucial for managing infantile PLAN.

Purpose of the Study:

• To prospectively characterize developmental milestone attainment and loss in children with infantile PLAN.
• To assess disease milestone acquisition and its association with quality of life.
• To establish disease norms for clinical reference and interventional trial design.

Main Methods:

• A prospective, observational, longitudinal natural history study involving 40 children with infantile PLAN.
• Analysis of developmental and disease milestones using histograms and Kaplan-Meier curves.
• Health-related quality of life assessed using the Infant Toddler Quality of Life Questionnaire (ITQOL-97) and analyzed with mixed-effects linear regression.

Main Results:

• Children with infantile PLAN retained some vocal and social milestones but rarely achieved walking.
• Quality of life scores, particularly 'physical abilities,' showed significant decline with age compared to a US reference population.
• All ITQOL-97 domains, except 'general behavior,' differed significantly from the reference population.

Conclusions:

• This study provides the first prospective characterization of developmental and disease milestones in infantile PLAN.
• Longitudinal quality of life data reveal significant age-related changes, especially in physical abilities.
• The findings offer essential disease norms for clinical practice and future therapeutic trial development.