title: Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency.
abstract: A retrospective, multicenter study of 180 children with cytochrome c oxidase (COX) deficiency analyzed the clinical features, prognosis, and molecular bases of the COX deficiency. Clinical symptoms including failure to thrive, encephalopathy, hypotony, Leigh syndrome, cardiac involvement, and hepatopathy appeared in most patients early after birth or in early childhood. Two thirds of all children died. Biochemical examination revealed an isolated COX deficiency in 101 children and COX deficiency combined with disturbances of other respiratory chain complexes in 79 children. Blood and cerebrospinal fluid lactate increased in 85% and 81% of examined cases, respectively. Pathogenic mutations in mitochondrial or nuclear DNA were established in 75 patients. Mutations in surfeit locus protein 1 gene (SURF1) were found in 47 children with Leigh syndrome; 2bp deletion 845-846delCT was found in 89% of independent alleles. Mutations in a mitochondrial copper-binding protein (SCO2) gene were found in nine children with encephalomyopathy and/or cardiomyopathy; all of them were homozygotes or heterozygotes for 1541G>A mutation. Different mitochondrial DNA (mtDNA) deletion or depletion were found in nine children, mtDNA mutation 3243A>G in six, mtDNA mutation 8363G>A in two children with Leigh syndrome and mtDNA mutations 8344A>G, and 9205-9206delTA in one child each. COX deficiency represents a heterogeneous group of diseases with unfavorable prognosis. Marked prevalence of two nuclear DNA mutations (845-846delCT in the SURF1 gene and 1541G>A in the SCO2 gene) associated with COX deficiency in a Slavonic population suggests the existence of regional differences in the genetic basis of COX deficiency.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Böhm
authors.forename: Ewa
authors.initials: E
authors.lastname: Pronicka
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Karczmarewicz
authors.forename: Maciej
authors.initials: M
authors.lastname: Pronicki
authors.forename: Dorota
authors.initials: D
authors.lastname: Piekutowska-Abramczuk
authors.forename: Jolanta
authors.initials: J
authors.lastname: Sykut-Cegielska
authors.forename: Hanna
authors.initials: H
authors.lastname: Mierzewska
authors.forename: Hana
authors.initials: H
authors.lastname: Hansikova
authors.forename: Katerina
authors.initials: K
authors.lastname: Vesela
authors.forename: Marketa
authors.initials: M
authors.lastname: Tesarova
authors.forename: Hana
authors.initials: H
authors.lastname: Houstkova
authors.forename: Josef
authors.initials: J
authors.lastname: Houstek
authors.forename: Jiri
authors.initials: J
authors.lastname: Zeman
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins; D002648:Child; D002675:Child, Preschool; D030401:Cytochrome-c Oxidase Deficiency / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D018153:Czech Republic; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D009154:Mutation; D011044:Poland; D011379:Prognosis; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D018154:Slovakia
chemical_list: D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D011506:Proteins; C400285:SCO2 protein, human; C092928:Surf-1 protein