Leigh syndrome with cytochrome-c oxidase deficiency and a single T insertion nt 5537 in the mitochondrial tRNATrp gene.
We report a nine-year-old boy with the features of Leigh syndrome (LS) and a severe cytochrome-c oxidase (COX) deficiency with a single thymidine insertion at nucleotide position 5537 (T 5537i) in the tRNA Trp gene of mitochondrial DNA. During infancy the boy was irritable and hypotonus was noticed. Early motor development was delayed, although mental development seemed normal until eight months of age. Early neurological signs were nystagmus, hypertonus and optic atrophy. Severe seizures and mental retardation developed subsequently. Major findings on neuroradiological investigation were from the brainstem, thalami and white matter compatible with LS. Spectrophotometric analysis of skeletal muscle mitochondria showed a profound COX deficiency and a marked complex I deficiency. Enzyme-histochemical analysis showed reduced COX activity in the majority of the muscle fibres. There were no ragged red fibres. The T 5537i mutation was found in a high proportion (> 95 %) in blood, liver and muscle tissue of the patient and in blood of the patient's mother (81 %). This mutation has previously been described in one family in which one child had a very high proportion of the T 5537i mutation and clinical features of LS. We conclude that, although mtDNA mutations are considered to be rare in LS with COX deficiency, the T 5537i mutation should be screened for in cases of LS with COX deficiency when SURF1 gene mutations have been excluded, especially when complex I activity is also decreased.
Tulinius
M
M
Department of Pediatrics, The Queen Silvia Children's Hospital, Göteborg, Sweden. mar.tulinius@vgregion.se
Moslemi
A-R
AR
Darin
N
N
Westerberg
B
B
Wiklund
L-M
LM
Holme
E
E
Oldfors
A
A
D002648:Child; D030401:Cytochrome-c Oxidase Deficiency / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007888:Leigh Disease / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D016254:Mutagenesis, Insertional / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012364:RNA, Transfer, Trp / Q000235:genetics*; D013942:Thymine Nucleotides / Q000235:genetics*
D000077278:RNA, Mitochondrial; D012364:RNA, Transfer, Trp; D013942:Thymine Nucleotides; D012313:RNA