Thesis defense Federica Conte (Donders series 590)

Phosphoglucomutase 1 deficiency: from clinical presentation to sugar metabolism in cell models

The scope of this thesis is to investigate the clinical presentation, progression, and metabolic management of phosphoglucomutase 1 (PGM1) deficiency, while establishing new analytical methods to enable the investigation of its tissue-specific pathogenesis. The central aim of this project is divided in three key objectives. A disease-driven objective focused on raising awareness about the clinical presentation of PGM1 deficiency, evaluating galactose-based metabolic management, and testing a new screening method to enable neonatal diagnosis (Chapters 1-3). A methodological objective focused on developing novel analytical methods for tissue-specific investigations of the sugar metabolism in cell and tissue models (Chapters 4-5). An applicational objective focused on the application of such methods on in vitro models to dissect the metabolic mechanisms underlying PGM1 deficiency (Chapters 5-6). Lastly, we discussed and contextualized our key findings with the most recent developments of our project and the current clinical and preclinical knowledge on PGM1 deficiency (Chapter 7).