Genotypes and Clinical Phenotypes in Children with Cytochrome-c Oxidase Deficiency

N. Darin; A.-R. Moslemi; S. Lebon; P. Rustin; E. Holme; A. Oldfors; M. Tulinius

doi:10.1055/s-2003-44670

Neuropediatrics, Table of Contents

Neuropediatrics 2003; 34(6): 311-317
DOI: 10.1055/s-2003-44670

Original Article

Georg Thieme Verlag Stuttgart · New York

Genotypes and Clinical Phenotypes in Children with Cytochrome-c Oxidase Deficiency

N. Darin¹ , A.-R. Moslemi² , S. Lebon³ , P. Rustin³ , E. Holme⁴ , A. Oldfors² , M. Tulinius¹

¹Department of Pediatrics, Sahlgrenska University Hospital, Göteborg, Sweden
²Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden
³INSERM U393, Hôpital Necker Enfants-Malades, Paris, France
⁴Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden

Abstract

Cytochrome c oxidase (COX) deficiency has been associated with a wide spectrum of clinical features and may be caused by mutations in different genes of both the mitochondrial and the nuclear DNA. In an attempt to correlate the clinical phenotype with the genotype in 16 childhood cases, mtDNA was analysed for deletion, depletion, and mutations in the three genes encoding COX subunits and the 22 tRNA genes. Furthermore, nuclear DNA was analysed for mutations in the SURF1, SCO2, COX10, and COX17 genes and cases with mtDNA depletion were analysed for mutations in the TK2 gene. SURF1-mutations were identified in three out of four cases with Leigh syndrome while a mutation in the mitochondrial tRNA^trp gene was identified in the fourth. One case with mtDNA depletion had mutations in the TK2 gene. In two cases with leukoencephalopathy, one case with encephalopathy, five cases with fatal infantile myopathy and cardiomyopathy, two cases with benign infantile myopathy, and one case with mtDNA depletion, no mutations were identified. We conclude that COX deficiency in childhood should be suspected in a wide range of clinical settings and although an increasing number of genetic defects have been identified, the underlying mutations remain unclear in the majority of the cases.

Key words

Cytochrome-c oxidase deficiency - SURFI - tRNA^trp - mtDNA depletion - TK2

Full Text

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Dr. Niklas Darin

The Queen Silvia Hospital for Children
Department of Pediatrics
Sahlgrenska University Hospital-East
Göteborg University

416 85 Göteborg

Sweden

Email: niklas.darin@medfak.gu.se