A CASE OF KEARNS-SAYRE SYNDROME SHOWING A CONSTANT PROPORTION OF DELETED MITOCHONDRIAL-DNA IN BLOOD-CELLS DURING 6 YEARS OF FOLLOW-UP

Kearns-Sayre syndrome (KSS) and Pearson syndrome (PS) show quite diffe rent phenotypes despite the same underlying genetic defect, i.e. a lar ge deletion of one population of mitochondrial (mt) DNA. The main feat ure of KSS is progressive encephalomyopathy; on the other hand, PS sho ws fatal hematological problems in early infancy. Through Southern blo t analysis of mtDNA of blood cells, deletion has been consistently fou nd in patients with PS but usually undetectable in KSS patients. There fore, their different clinical phenotypes have been explained by the d ifferent tissue distribution of mutant mtDNA. Recently, a few cases we re reported which had features of PS in infancy and later developed KS S. These observations suggest that phenotypes may also be modified by the selection process involving mtDNA within different tissues. We fou nd a case of KSS, who initially presented endocrinological dysfunction such as insulin-dependent diabetes mellitus (IDDM) and growth hormone (GH) deficiency, and had not developed external ophthalmoplegia until the age of 17. Although he did not show any symptoms of PS, a marked proportion of mtDNA was deleted not only in muscle but also in blood c ells. Analysis of his blood cells showed an unchanged proportion of de leted mtDNA at three estimations within 6 years of the follow-up perio d. This case provides evidence that deleted mtDNA in blood cells also has a stable replicative capacity and that a large proportion of delet ed mtDNA in blood cells may not accompany hematological problems. (C) 1998 Elsevier Science B.V.