KEARNS-SAYRE SYNDROME-ASSOCIATED WITH MITOCHONDRIAL-DNA DELETION OR DUPLICATION - A MOLECULAR-GENETIC AND PATHOLOGICAL-STUDY

The neuropathological findings in 2 patients with Kearns-Sayre syndrom e and mitochondrial DNA (mtDNA) rearrangements, one a predominant dele tion and the other a predominant duplication, were remarkably similar, showing diffuse vacuolation of white matter. There were some of the p athological features of Leigh's syndrome in the spinal cord of the pat ient with a duplication. In the patient with a predominant deletion, r earranged mtDNA was undetectable in blood, spleen, and testis, and pre sent in highest amounts in muscle and the brain, but relatively low in cerebellum, reflecting the ratio seen, albeit in much smaller amounts , in normal aged brains. MtDNA rearrangements in this patient were lar gely deletions or deletion dimers; duplicated mtDNA was present in onl y trace amounts in some tissues and there was none in skeletal muscle. The patient with a predominant duplication of mtDNA had higher amount s of rearranged mtDNA in blood (mainly duplicated) than muscle (mainly deleted). Correlation of these data with tissue dysfunction is probab ly complicated by the replicative behaviour of deleted, duplicated and normal mtDNA.