Acute Nutritional Ketosis in GSD IIIa

Acute Nutritional Ketosis and Exercise in Glycogen Storage Disease Type IIIa

The investigators will study if acute nutritional ketosis in adult GSD IIIa patients can boost muscle mitochondrial function in vivo.

Glycogen Storage Disease type IIIa (GSD IIIa) is an inborn error of carbohydrate metabolism caused by impaired glycogen debranching enzyme (GDE) activity. The ageing GSD IIIa cohort shows that muscle involvement -despite dietary management- is a common disabling phenotype in adulthood. Currently, no specific therapy has been established for muscle problems in adult GSD IIIa patients.

However, it could be hypothesized that nutritional ketosis (NK) will be highly beneficial to patients. Amongst others, ketone bodies could take on the role of primary energy source in exercising muscle. Recently, acute NK in exercise was studied in humans. NK was found to enhance muscle mitochondrial function in athletes.

The investigators will study if acute NK in adult GSD IIIa patients can boost muscle mitochondrial function in vivo.

Inclusion Criteria:

• GSD III confirmed with enzyme assay and/or AGL mutation analysis and GSD IIIa further specified as deficient debranching enzyme activity in muscle or clinical and/or biochemical signs of cardiac and/or skeletal muscular involvement.

Exclusion Criteria:

• contraindications for MRI studies (assessed by standardised questionnaire)
• inability to perform bicycle exercise.
• intercurrent illness which may influence exercise tolerance (anemia, musculoskeletal injury, or other undiagnosed illness under investigation).
• known coronary artery disease, positive history for angina or cardiomyopathy.
• insulin-dependent diabetes mellitus.
• loss of, or an inability to give informed consent.
• pregnancy or current breastfeeding.
• any other cause which in the opinion of the investigators, may affect the participant's ability to participate in the study