title: Severe mitochondrial cytopathy with complete A-V block, PEO, and mtDNA deletions.
abstract: We describe a 17-year-old male with neurologic and cardiovascular disorders characterized by complete atrioventricular block and a mitochondrial cytopathy with clinical, structural, biochemical, and molecular features shared by chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. The patient's manifestations included progressive external ophthalmoplegia, bilateral ptosis, muscle weakness, delayed development, and progressive hearing loss with multiple mitochondrial DNA deletions, including an abundant 11-kb novel deletion and reduced specific activities of respiratory complexes I, III, and IV present in skeletal muscle. Ultrastructural analysis of biopsied muscle revealed a heterogenous mixture of normal and abnormal mitochondria with unusual cristae. This unique mitochondrial DNA deletion, which eliminates the origin of mitochondrial DNA replication for the light strand, may be responsible for generating an intermediate clinical phenotype.
authors.affiliation: Molecular Cardiology and Neuromuscular Institute, Highland Park, New Jersey 08904, USA.
authors.forename: José
authors.initials: J
authors.lastname: Marín-García
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Goldenthal
authors.forename: Laura
authors.initials: L
authors.lastname: Flores-Sarnat
authors.forename: Harvey B
authors.initials: HB
authors.lastname: Sarnat
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D030401:Cytochrome-c Oxidase Deficiency / Q000175:diagnosis / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D003937:Diagnosis, Differential; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III / Q000172:deficiency / Q000235:genetics; D006327:Heart Block / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000473:pathology; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency / Q000235:genetics; D010641:Phenotype
chemical_list: D004272:DNA, Mitochondrial; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III