Neurodegenerative Diseases in Children: A Comprehensive Review

Area of Science:

• Neuroscience
• Genetics
• Metabolic Disorders

Background:

• Pediatric neurodegenerative diseases (NDDs) are rare but collectively significant, characterized by progressive neurological decline and developmental regression.
• Unlike adult NDDs, pediatric forms are primarily genetic, stemming from defects in cellular pathways like lysosomal degradation and mitochondrial function.

Purpose of the Study:

• To review current knowledge on the epidemiology, molecular classification, pathophysiology, and therapeutic strategies for major pediatric neurodegenerative disorders.
• To highlight the importance of early molecular diagnosis and emerging mechanism-based interventions.

Main Methods:

• Comprehensive literature review synthesizing epidemiological data, molecular classifications, and pathophysiological mechanisms.
• Discussion of advances in next-generation sequencing, metabolic profiling, and neuroimaging for diagnosis.
• Analysis of current and emerging therapeutic strategies, including enzyme replacement, stem cell transplantation, and gene therapy.

Main Results:

• Pediatric NDDs represent a 'rare-but-many' landscape with a measurable population burden.
• Converging pathophysiological processes include toxic substrate accumulation, impaired autophagy-lysosome flux, and mitochondrial dysfunction.
• Advances in diagnostics enable earlier detection, crucial for presymptomatic interventions.

Conclusions:

• Early molecular diagnosis is critical for optimizing outcomes in pediatric neurodegenerative diseases.
• Therapeutic approaches are evolving towards mechanism-based interventions, including gene therapy.
• Multidisciplinary, precision-based strategies integrating genomic medicine are essential for improved classification, prognostication, and treatment access.