G8363A mitochondrial DNA mutation is not a rare cause of Leigh syndrome - clinical, biochemical and pathological study of an affected child.
Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, having relatively homogeneous clinical symptomatology and pattern of neuropathological changes, shows remarkable heterogeneity in biochemical and molecular background. G8363A mitochondrial DNA mutation typical for MERRF syndrome and progressive cardiomyopathy may also be associated with LS. Clinical, biochemical and pathological findings in a boy aged 28 months who died with classical COX-deficientLSassociatedwithmtG8363Aisdescribedindetail.Hyperlactataemia,LCHAD-like organic acids profile and respiratory alkalosis(pH7.47,pCO2 4.9 mmHg, HCO3 3.0 mmol/l) were observed. Spectrophotometric assay showed deficit of respiratory chain complexes IVand I. Skeletal muscle biopsy revealed mosaic cytochrome oxidase deficit,lipid accumulation and ultrastructural abnormalities of mitochondria. Postmortem examination confirmed the presence of typical LS central nervous system lesions as well as hypertrophy of the left ventricle of the heart.


CONCLUSIONS
mtG8363A "MERRF-like" mutation should be included in the differential diagnosis of classical LS in infants. This case is in agreement with our hypothesis that hyperventilation plays a substantial role in progression of central nervous system damage.
Pronicki
Maciej
M
Department of Pathology, The Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland. empronicki@poczta.onet.pl
Sykut-Cegielska
Jolanta
J
Matyja
Ewa
E
Musialowicz
Jacek
J
Karczmarewicz
Elzbieta
E
Tonska
Katarzyna
K
Piechota
Janusz
J
Piekutowska-Abramczuk
Dorota
D
Kowalski
Pawel
P
Bartnik
Ewa
E
D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007888:Leigh Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation
D004272:DNA, Mitochondrial