Glycogen storage disease type IIIa (GSDIIIa) is an inherited disorder of glycogen degradation caused by deficient activity of glycogen debranching enzyme in liver and muscle tissue. GSDIIIa patients mostly present with hepatomegaly, fasting intolerance, and failure to thrive during childhood. This thesis elaborated on the natural history, different monitoring tools and alternative dietary strategies in GSDIIIa patients.
The international, multi-center cohort study demonstrated that the GSDIIIa phenotype shifts from an acute fasting-intolerance and liver specific phenotype in childhood, to a progressive muscle phenotype in adulthood. Retrospective analysis of fasting studies emphasized the importance of incidental ketone body monitoring. Also, the design, validation and first implementation process of a telemedicine platform for patients and healthcare professionals was illustrated. As part of this platform, a module for emergency protocols generation was created. A retrospective chart review concluded that emergency protocols can be safe and effective for home management by the caregivers and the first hour in-hospital management.
Published and novel cases were collected in an international cohort study to examine evidence of dietary lipid manipulations in hepatic GSD patients. Results suggest that a high fat diet could be considered in pediatric GSDIIIa patients who develop hypertrophic cardiomyopathy on the traditional diet. Finally, a 31P-MRS study with a ketone-ester drink showed in vivo evidence that acute nutritional ketosis has a beneficial effect on muscle energy balance during exercise in GSDIIIa patients with a severe muscle phenotype. All of this has opened doors for future studies regarding precision medicine for the individual GSDIIIa patient.