Congenital Hypoplastic Anemia, Diabetes, and Severe Renal Tubular Dysfunction Associated with a Mitochondrial DNA Deletion

ABSTRACT. Mitochondrial DNA (mtDNA) deletion is associated with a variety of clinical entities. In addition to progressive external ophthalmoplegia and Kearns-Sayre syndrome, mtDNA deletions have been demonstrated in Pearson's syndrome. We report an mtDNA deletion in an infant with a variant of Pearson's syndrome. Not only does she have congenital anemia, severe tubulopathy, and exo- crine pancreas insufficiency, but she also has diabetes and cerebral atrophy. However, there are no signs of gut or liver involvement. Bone marrow improved while new tis- sues were involved, thus showing variability in progression of the disease. Decreased respiratory chain enzyme activi- ties were demonstrated in muscle, and an mtDNA deletion was demonstrated in muscle, kidney, leukocytes, and fibro- blasts. (Pediatr Res 30: 327-330, 1991) Abbreviations cyt c, cytochrome c KSS, Kearns-Sayre syndrome mtDNA, mitochondrial DNA PCR, polymerase chain reaction Mitochondrial dysfunction has been described in a heteroge- neous group of clinical entities varying from benign ocular myopathy to fatal encephalomyopathy and multisystem disor- ders of organs with a high energy demand. Typically, "ragged- red-fibers" are found in modified Comori-trichrome stained muscle biopsies and abnormal mitochondria in electron micros- copy of affected tissues. Defects are demonstrated in several biochemical pathways of energy production, most frequently in the mitochondrial respiratory chain enzymes, which are encoded both by nuclear and mitochondrial genes. A large deletion of human mtDNA in patients with mitochondria1 myopathies was first described by Holt et al. (1). This has led to new possibilities in diagnosing and classifying mitochondrial diseases. Deletions have been found in patients with progressive external ophthal- moplegia (2) and KSS (3, 4). In addition to these clinical entities, deletions have been reported in one patient with pancytopenia (5) and in Pearson's syndrome (6, 7). We now report a 2-yr-old child with severe renal tubular dysfunction, pancreatic insuffi- ciency. diabetes, cerebral atrophy, and recovery from congenital