PhD defence Raquel Sonata Asmaradewi van Gool

Keywords: Lysosomal storage diseases, Brain–body interaction, Biomarkers, Brain networks

"From Cells to Circuits: Transdiagnostic Mechanisms of Dysfunction in Pompe Disease and Niemann-Pick Disease Type C"

This PhD thesis investigated how rare genetic metabolic diseases affect daily functioning by disrupting shared brain–body circuits. It focused on Pompe disease, which has traditionally been viewed as a muscle disorder, and Niemann-Pick disease type C, a condition known for its significant involvement of the central nervous system. Using brain imaging, speech analysis, muscle measurements, and clinical assessments, this research showed that changes in movement, speech, and cognition are closely linked to alterations in specific brain networks.

Importantly, similar neural circuits were affected across different rare diseases and overlapped with circuits implicated in more common neurological and psychiatric conditions. This highlights a bidirectional relationship: rare diseases offer clear models to study brain dysfunction, while insights from broader brain research help interpret symptoms and progression in small patient populations.

By identifying non-invasive, patient-friendly biomarkers, this work supports earlier recognition of disease-related brain involvement. This is particularly relevant for conditions such as Niemann-Pick disease type C, where the average delay to diagnosis is approximately seven years, and earlier detection could substantially improve patient care and quality of life.

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