Impairmenxs of the Mitochondrial Energetic Metabolism in Patients with Kearns-Sayre Syndrome

Overview

Background.
Kearns-Sayre syndrome is a multisystem disorder caused by rearrangements of mitochondrial genome including various deletions and/or duplications. The aim of the study is to analyse the impact of mitochondrial DNA (mtDNA) deletions on the mitochondrial energetic metabolism in %ve patients with Kearns-Sayre syndrome. Methoda and Results. The course of the disease is progressive in all patients. All of them have bilateral ptosis and external opthalmoplegia, four have retinitis pigmentosa, three have progressive muscle weakness and three have pacemaker because of complete A-V heart block. One patient underwent renal transplantation at the age of 12 because of a chronic renal failure. Southern blot analysis in muscle tissue revealed large scale heteroplasmic mtDNA deletions (3-7.4 kb) in all patients, the number of mutated copies of mtDNA ranged from 50 to 70 %. Spectrophotometric measurements of respiratory chain complexes activities in muscle tissue revealed various combinations of defects of complex III, IV and I+III activities in all patients. Nevertheless, the lactic acidosis was permanently present only in one patient. Ragged-red %bera esere found in two patients.Conclusions. Although the diagnostic of Kearns-Sayre syndrome is based on clinical features, molecular analysis of mtDNA is necessary to confirm the diagnosis. The prognosis of the disease is unfavourable and co-operation between the patient and various specialista is necessary for the treatment, which is currently only symptomatic.

Key words:
Kearns-Sayre syndrome, mtDNA deletion, respiratory chain complexes.