Loss of myelin-associated glycoprotein in kearns-sayre syndrome.

OBJECTIVE To explore myelin components and mitochondrial changes within the central nervous system in patients with well-characterized mitochondrial disorders due to nuclear DNA or mitochondrial DNA (mtDNA) mutations. DESIGN Immunohistochemical analysis, histochemical analysis, mtDNA sequencing, and real-time and long-range polymerase chain reaction were used to determine the pathogenicity of mtDNA deletions. SETTING Department of Clinical Pathology, Columbia University Medical Center, and Newcastle Brain Tissue Resource. PATIENTS Seventeen patients with mitochondrial disorders and 7 controls were studied from August 1, 2009, to August 1, 2010. MAIN OUTCOME MEASURE Regions of myelin-associated glycoprotein (MAG) loss. RESULTS Myelin-associated glycoprotein loss in Kearns-Sayre syndrome was associated with oligodendrocyte loss and nuclear translocation of apoptosis-inducing factor, whereas inflammation, neuronal loss, and axonal injury were minimal. In a Kearns-Sayre syndrome MAG loss region, high levels of mtDNA deletions together with cytochrome- c oxidase-deficient cells and loss of mitochondrial respiratory chain subunits (more prominent in the white than gray matter and glia than axons) confirmed the pathogenicity of mtDNA deletions. CONCLUSION Primary mitochondrial respiratory chain defects affecting the white matter, and unrelated to inflammation, are associated with MAG loss and central nervous system demyelination.