Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency
Child; Female; Humans; infant; Male; Prognosis; Mutation; adolescent; Preschool; infant; Q3 Literature Search; Newborn; DNA; Mitochondrial/genetics; Proteins/genetics; Sequence Deletion; Membrane Proteins; Mitochondrial Proteins; Carrier Proteins; Cytochrome-c Oxidase Deficiency/diagnosis/genetics/mortality; Czech Republic; Poland; Slovakia
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.
2006
Bohm M; Pronicka E; Karczmarewicz E; Pronicki M; Piekutowska-Abramczuk D; Sykut-Cegielska J; Mierzewska H; Hansikova H; Vesela K; Tesarova M; Houstkova H; Houstek J; Zeman J
Pediatric Research
2006
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1203/01.pdr.0000190572.68191.13" target="_blank" rel="noreferrer">10.1203/01.pdr.0000190572.68191.13</a>
Unusual clinical presentations in four cases of Leigh disease, cytochrome C oxidase deficiency, and SURF1 gene mutations
Female; Humans; infant; Male; Phenotype; infant; Q3 Literature Search; Newborn; DNA Mutational Analysis; Muscle; Skeletal/pathology; Proteins/genetics; Frameshift Mutation; Cytochrome-c Oxidase Deficiency/complications/genetics/pathology; Kidney Diseases/etiology; Leigh Disease/complications/genetics/pathology; Membrane Proteins; Mitochondrial Proteins
Mutations in the SURF1 gene are the most frequent causes of Leigh disease with cytochrome c oxidase deficiency. We describe four children with novel SURF1 mutations and unusual features: three had prominent renal symptoms and one had ragged red fibers in the muscle biopsy. We identified five pathogenic mutations in SURF1: two mutations were novel, an in-frame nonsense mutation (834G-->A) and an out-of-frame duplication (820-824dupTACAT). Although renal manifestations have not been described in association with SURF1 mutations, they can be part of the clinical presentation. Likewise, mitochondrial proliferation in muscle (with ragged red fibers) is most unusual in Leigh disease but might be part of an emerging phenotype.
2005
Tay SK; Sacconi S; Akman HO; Morales JF; Morales A; De Vivo DC; Shanske S; Bonilla E; DiMauro S
Journal Of Child Neurology
2005
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1177/08830738050200080701" target="_blank" rel="noreferrer">10.1177/08830738050200080701</a>