The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases

The investigators will study 10 children with mitochondrial diseases and 10 healthy control children. The investigators will study control children to be able compare the results of children with mitochondrial diseases to control healthy children. Therefore, the investigators will study control children only once to compare these results to the results of children with mitochondrial diseases at baseline. To assess the effect of arginine and citrulline on children with mitochondrial diseases, the investigators need to assess children with mitochondrial diseases four times. First time as baseline. Then children with mitochondrial diseases will be randomized to receive either oral arginine or citrulline at a dose of 500 mg/kg/day divided in 3 doses daily for 2 weeks after which a second assessment will be performed. Oral arginine or citrulline will be discontinued and after a two-week washout period another baseline assessment will be done. After that, the child will be started on oral citrulline (if the participant received arginine the first time) or arginine (if the participant received citrulline the first time) at a dose of 500 mg/kg/day divided in 3 doses daily for 2 weeks after which a fourth assessment will be done.

Inclusion criteria

• Diagnosis of mitochondrial disease with multi-organ disease involving neurological and/or muscular systems.
• The diagnosis must be confirmed either molecularly (identifying mutations known to be associated with mitochondrial diseases) or by respiratory chain assay abnormalities.

Exclusion criteria

• Have acute illness or physical disability interfering with ability to undergo the study procedures.
• Known to have other factors that are known to result in endothelial dysfunction including hypertension, hyperlipidemia, and diabetes.