To identify the cause of an adult-onset multisystemic disease with multiple deletions of mitochondrial DNA (mtDNA).
A 65-year-old man with axonal sensorimotor peripheral neuropathy, ptosis, ophthalmoparesis, diabetes mellitus, exercise intolerance, steatohepatopathy, depression, parkinsonism, and gastrointestinal dysmotility.
Skeletal muscle biopsy revealed ragged-red and cytochrome- c oxidase–deficient fibers, and Southern blot analysis showed multiple mtDNA deletions. No deletions were detected in fibroblasts, and the results of quantitative polymerase chain reaction showed that the amount of mtDNA was normal in both muscle and fibroblasts. Exome sequencing using a mitochondrial library revealed compound heterozygous MPV17 mutations (p.LysMet88-89MetLeu and p.Leu143*), a novel cause of mtDNA multiple deletions.
In addition to causing juvenile-onset disorders with mtDNA depletion, MPV17 mutations can cause adult-onset multisystemic disease with multiple mtDNA deletions.