pediatrics
Mitochondrial Oxidative Phosphorylation Disorders
Kearns Sayre syndrome and chronic progressive external ophthalmoplegia (CPEO)
These disorders are characterized by ophthalmoplegia, ptosis, atypical retinitis pigmentosa, ragged-red fiber myopathy, ataxia, deafness, and cardiomyopathy typically occurring before age 20 years. Kearns-Sayre syndrome is caused by a large contiguous deletion in mtDNA that results in the loss of genes important for mitochondrial protein formation and oxidative phosphorylation. CPEO can result from mutations in one of several different nuclear genes that are critical for the production and maintenance of mtDNA and result in the deletion of large segments of mtDNA in muscle cells. Less common causes involve point mutations in mtDNA genes that provide instructions for making molecules called transfer RNAs. 