2.1. Leigh syndrome

More than 80 different SURF1 gene mutations have been identified in people with Leigh syndrome, a progressive brain disorder that usually appears in infancy or early childhood. Affected children may experience delayed development, muscle weakness, problems with movement, or difficulty breathing.

Approximately 10 to 15 percent of people with Leigh syndrome have a mutation in the SURF1 gene. Most SURF1 gene mutations result in an abnormally short protein. Other mutations replace a single protein building block in the SURF1 protein. The mutated proteins are broken down in the cell, which results in the absence of SURF1 protein. Lack of SURF1 protein hinders the proper formation of the COX complex. As a result, COX enzyme activity is severely reduced, which leads to impaired oxidative phosphorylation.

Although the exact mechanism is unclear, researchers believe that impaired oxidative phosphorylation can lead to cell death because of decreased energy available in the cell. Certain tissues that require large amounts of energy, such as the brain, muscles, and heart, seem especially sensitive to decreases in cellular energy. Cell death in the brain likely causes the characteristic changes in the brain seen in Leigh syndrome, which contribute to the signs and symptoms of the condition. Cell death in other sensitive tissues may also contribute to the features of Leigh syndrome.