Abstract

A patient is described who has features of Pearson syndrome and who presented in the neonatal period with a hypoplastic anemia. He later developed hepatic, renal, and exocrine pancreatic dysfunction. At the age of 5 years he developed visual impairment, tremor, ataxia, proximal muscle weakness, external ophthalmoplegia, and a pigmentary retinopathy (Kearns-Sayre syndrome). Muscle biopsy confirmed the diagnosis of mitochondrial myopathy. Analysis of mtDNA from leukocytes and muscle showed mtDNA heteroplasmy in both tissues, with one population of mtDNA deleted by 4.9 kb. The deleted region was bridged by a 13-nucleotide sequence occurring as a direct repeat in normal mtDNA. Both Pearson syndrome and Kearns-Sayre syndrome have been noted to be associated with deletions of mtDNA; they have not previously been described in the same patient. These observations indicate that the two disorders have the same molecular basis; the different phenotypes are probably determined by the initial proportion of deleted mtDNAs and modified by selection against them in different tissues.