Kearns-Sayre syndrome: oncocytic transformation of choroid plexus epithelium

Kearns-Sayre syndrome (KSS) is a sporadic multisystem disorder due to a def ect of oxidative phosphorylation and associated with clonally-expanded rear rangements of mitochondrial DNA (mtDNA) deletions (Delta-mtDNAs) and/or dup lications (dup-mtDNAs). To gain further insight into the pathogenesis of CN S dysfunction in KSS, we studied the choroid plexus from two autoptic cases using in situ hybridization (ISH) of mtDNA, and immunohistochemistry to de tect mtDNA and nuclear DNA-encoded subunits of the respiratory chain. Neuro pathological examination of both cases showed oncocytic transformation of c horoid plexus epithelial cells. In the same cells, ISH demonstrated that th e predominant species of mtDNA were Delta-mtDNAs, and immunohistochemistry showed a decreased expression of mtDNA-encoded proteins. We suggest that mi tochondrial abnormalities due to the presence of abundant Delta-mtDNAs in t he choroid plexus play an important role in causing the increased cerebrosp inal fluid (CSF) protein and reduced folic-acid levels that are characteris tic of KSS. (C) 2000 Elsevier Science B.V. All rights reserved.