MELAS patients suffer from exercise intolerance, weakness, poor vision or blindness, poor growth, developmental delay, and deafness. They also have unique 'stroke-like' episodes (SLEs) which are not due to blockages of large or medium arteries. These 'strokes' are thought to be due to energy failure of very small brain blood vessels combined with energy failure in the mitochondria (cell battery) of the brain cells, especially in the back region of the brain in the vision centre. This leads to visual loss and paralysis. The overall goal of this study is to better understand the mechanism of these SLEs at the level of the brain cells and small blood vessels.
Description: We will study exercising quadriceps using our MR-compatible up-down ergometer and our well established aerobic exercise protocol at 65 % of maximal voluntary contraction.Measure: Muscle function investigation via 31P-Magnetic resonance spectroscopy Time: 60 to 105 minutes post dose
Description: Maximal incremental cycle ergometry is conducted in our CardioRespiratory Exercise Lab at HSC by our established protocols (26). Serum CK and quantitative AA (for arginine, ornithine and citrulline) will be measured pre- and post- exercise as well as eNO in order to correlate aerobic exercise parameters with serum arg and eNO levels..Measure: Total body maximal aerobic capacity Time: 60-75 mins post dose
Description: Functional MRI-Blood oxygen level dependent (BOLD) of brainMeasure: CerebroVascular Reactivity Time: 75-105 mins post dose
Description: eNO will be measured using single breath on-line measurements for the assessment of lower airway Nitric OxideMeasure: Exhaled Nitric Oxide (eNO) Time: 75 mins pre dose, 75 mins post dose
There is one SNP
Inclusion Criteria: Experimental Siblings with MELAS (A3243G) syndrome - 17-23 years - Followed Neurometabolic Clinic at the Hospital for Sick Children will be studied. --- A3243G ---