Mitochondrial Genetic disorders

The mitochondria are the cell’s suppliers of energy, and it is not surprising that the organs that are most affected by the presence of abnormal mitochondria are those that have the greatest energy requirements, such as the brain, muscle, heart, and liver. Common manifestations include developmental delay, seizures, cardiac dysfunction, decreased muscle strength and tone, and hearing and vision problems.

Mitochondrial diseases are one of the most common inborn errors of metabolism, with a conservative estimated prevalence of approximately 1:5,000

The first human disease that was associated with a mutation in mitochondrial DNA is called Leber’s Hereditary Optic Neuropathy, or LHON.  LHON causes a painless loss of central vision between 12 and 30 years of age. Both eyes are affected at the same time.

Large deletions in mitochondrial DNA cause a condition called Kearns-Sayre Syndrome. These deletions affect the mitochondria from doing their job of extracting energy. Kearns-Sayre Syndrome can cause symptoms such as weakness of the muscles, including those that control eyelid and eye movement, as well as degeneration of the retina and development of heart disease

Pearson syndrome is a mitochondrial disease caused by a deletion in mitochondrial DNA (mt DNA).I t is characterized by sideroblastic anemia and exocrine pancreas dysfunction. The deletions occur in one or more tRNA genes and are usually spontaneous . The deletions of mitochondrial DNA with Pearson syndrome ranges in size from 1.1 to 10 kilobases.

Leigh syndrome is a rare inherited neurometabolic disorder that affects the central nervous system (brain, spinal cord, and optic nerve). This disorder begins in infants between the ages of 3 months and 2 years . Rarely, it can occur in teenagers and adults. Mutations in mitochondrial DNA (mtDNA) and over 30 genes in nuclear DNA have been implicated in Leigh disease. The most common of these mutations (in 10 to 20 percent of Leigh syndrome ) occurs in MT-ATP6. This gene codes for ATP synthase, an enzyme that directly generates ATP present in the last complex of the oxidative  phosphorylation chain. The most common MT-ATP6 mutation found with Leigh syndrome is a point mutation occurring  at nucleotide 8993. This mutation changes a thymine to a guanine

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