Kearns-Sayre syndrome: Unusual pattern of expression of subunits of the respiratory chain in the cerebellar system

Kearns-Sayre syndrome (KSS) is a sporadic multisystem disorder of oxidative phosphorylation associated with clonally expanded rearrangements of mitoch ondrial DNA (mtDNA). Mitochondrial dysfunction in the central nervous syste m of patients with KSS accounts for the neurological manifestations of the disease. To gain further insight into the pathogenesis of neuronal dysfunct ion in KSS, we used antibodies against mtDNA-encoded and nuclear DNA-encode d subunits of the mitochondrial respiratory chain to study the expression o f these proteins in the cerebellar cortex, dentate nucleus, and inferior ol ivary nucleus from 2 autoptic cases of KSS. Neuropathological examination s howed a moderate loss of Purkinje cells and spongiform degeneration of the cerebellar white matter. By using immunohistochemistry, we found a decrease d expression of mtDNA-encoded proteins only in neurons of the dentate nucle us. We suggest that mitochondrial abnormalities in the dentate nucleus in c onjunction with loss of Purkinje cells and spongiform degeneration of the c erebellar white matter may be important factors in the genesis of the cereb ellar dysfunction in KSS.