Abstract:
A young, adult, African male patient presented
with progressive proximal muscle weakness, external
ophthalmoplegia and ptosis, as well as cardiac conduction
abnormalities resembling Kearns–Sayre syndrome (KSS).
Magnetic resonance imaging (MRI) of the brain revealed
normal basal ganglia but bilateral well-circumscribed
lesions in the cerebellar peduncles. Enzyme deficiencies
in oxidative phosphorylation (OXPHOS) complexes I,
IV and V was measured in muscle tissue. Blue native
polyacrylamide gel electrophoresis (BN-PAGE) confirmed
decreased protein content and activity of these complexes
and revealed the presence of two catalytically active complex
V sub-complexes. Upon investigation by molecular genetics,
the mitochondrial DNA (mtDNA) copy number was found
to be elevated and a novel deletion of 3431 bp was found in
80% of muscle mtDNA between positions 7115 and 10546,
flanked by a 5 bp direct repeat sequence. In addition, it could
also be concluded that the absence of mtDNA-encoded
ATPase6 and ATPase8 genes in this patient clearly resulted
in aberrant synthesis of ATP synthase.
