title: "Bartter-like" phenotype in Kearns-Sayre syndrome.
abstract: Kearns-Sayre syndrome (KSS) is a mitochondrial disease caused by large deletions in mitochondrial DNA (mtDNA). In most patients the disease is characterized by mtDNA heteroplasmy, where a mixture of wild-type and mutated mtDNA co-exist within cells in variable proportion, modulating the severity of the phenotype in different tissues. We report on the case of a 14-year-old child with classical symptoms of KSS and a renal phenotype characterized by hypokalaemic alkalosis, hypomagnesaemia, hyperreninaemia, hyperaldosteronism and nephrocalcinosis, resembling Bartter syndrome. Analysis of mtDNA demonstrated an 8,661 bp deletion involving eight mitochondrial genes. Uneven degrees of mtDNA heteroplasmy were demonstrated in several tissues, ranging from 24% to 60% of deleted/total mtDNA. Variable degrees of expression of mitochondrial enzymes were also found in biopsy specimens of renal and skeletal muscle by histocytochemistry. In particular, preserved cytochrome c oxidase was observed in tubular structures within medullary rays. It is proposed that a "Bartter-like" phenotype can arise in some patients with KSS as a result of heteroplasmy. In these cases aldosterone-responsive tubular structures have been spared during renal embryogenesis, allowing for the development of hypokalaemic alkalosis in response to salt and water losses from the more damaged tubular segments.
authors.affiliation: Department of Nephrology and Urology, Division of Nephrology, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy. emma@opbg.net
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
authors.forename: Carla
authors.initials: C
authors.lastname: Pizzini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Giandomenico
authors.forename: Andrea
authors.initials: A
authors.lastname: Onetti-Muda
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Rizzoni
mesh_terms: D000138:Acidosis / Q000150:complications; D000293:Adolescent; D001477:Bartter Syndrome / Q000150:complications* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D007008:Hypokalemia / Q000150:complications; D007150:Immunohistochemistry; D007625:Kearns-Sayre Syndrome / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010641:Phenotype; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV