Neuropediatrics 2003; 34(2): 87-91
DOI: 10.1055/s-2003-39607
Original Article

Georg Thieme Verlag Stuttgart · New York

Leigh Syndrome with Cytochrome-c Oxidase Deficiency and a Single T Insertion nt 5537 in the Mitochondrial tRNATrp Gene

M. Tulinius 1 , A.-R. Moslemi 3 , N. Darin 1 , B. Westerberg 1 , L.-M. Wiklund 2 , E. Holme 4 , A. Oldfors 3
  • 1Departments of Pediatrics, The Queen Silvia Children's Hospital, Göteborg, Sweden
  • 2Department of Pediatric Radiology, The Queen Silvia Children's Hospital, Göteborg, Sweden
  • 3Departments of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden
  • 4Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden
Further Information

Publication History

Received: September 2, 2002

Accepted after Revision: February 24, 2003

Publication Date:
30 May 2003 (online)

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Abstract

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 (T5537i) in the tRNATrp 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 T5537i 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 T5537i mutation and clinical features of LS. We conclude that, although mtDNA mutations are considered to be rare in LS with COX deficiency, the T5537i 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.

References

M. D. PhD Már Tulinius

Department of Pediatrics
The Queen Silvia Children's Hospital, Sahlgrenska University Hospital

41685 Göteborg

Sweden

Email: mar.tulinius@vgregion.se