Childhood dementia (CD) is a collective term for rare paediatric conditions characterized by severe degeneration of the CNS. Around one in every 2,900 babies are born with a condition that causes CD. Around 21% of CD is caused by lysosomal storage disorders, a group of 70+ rare genetic conditions that cause a systemic build-up of toxic materials in cells. Although diagnosis of most LSDs is relatively well established, there is a need for prognostic biomarkers that can improve disease monitoring and assess therapeutic efficacy of new and proposed treatments. A reliable and easily administered blood test to assess neurodegeneration is currently a health care priority for people with CD. The main aim is to assemble a cohort of individuals with CD caused by LSDs and to assess their blood biomarkers at baseline and again at 1 year. This project proposes the use of state-of-art biomarker technologies for discovery of protein biomarkers of neurological decline in CD. This study also aims to investigate genes associated with neurodegeneration and identify differentially expressed genes in CD. Our analyses will evaluate the relationships between protein, gene biomarkers, and standard diagnostic markers to identify a disease signature associated with neurodegeneration. Additionally, this will evaluate if drugs targeting the autophagy-lysosomal pathway can alleviate disease phenotypes in a neuronal cell model of CD. Findings of this research will advance knowledge into the neurological deterioration and novel treatment strategies to alleviate neuronal damage and will reveal the overlapping disease mechanisms between the subgroups highlighting potential common therapeutic targets.