Multiple defects of the mitochondrial respiratory chain in a mitochondrial encephalopathy (MERRF): a clinical, biochemical and molecular study.
We describe a young man with a progressive neurological disorder including myoclonus, mental retardation, muscle weakness and a mitochondrial myopathy (myoclonus epilepsy and ragged red fibres--MERRF). Multiple abnormalities of the mitochondrial respiratory chain in skeletal muscle are shown by direct measurement of the flux through the individual complexes, low-temperature redox spectroscopy and decreased immunodetectable subunits of complexes I and IV by immunoblotting. No abnormality of mitochondrial DNA was found. This is the first report of combined defects of complexes I, III and IV as a cause of this clinical syndrome. However, we propose that the occurrence of multiple respiratory chain defects may be more common than previously recognised and that this particular combination of defects, involving complexes I, III and IV, may be the predominant biochemical abnormality in MERRF.
Bindoff
L A
LA
Division of Clinical Neuroscience, University of Newcastle upon Tyne, Medical School, U.K.
Desnuelle
C
C
Birch-Machin
M A
MA
Pellissier
J F
JF
Serratrice
G
G
Dravet
C
C
Bureau
M
M
Howell
N
N
Turnbull
D M
DM
D000328:Adult; D002524:Cerebellar Ataxia / Q000201:enzymology / Q000235:genetics*; D002675:Child, Preschool; D030401:Cytochrome-c Oxidase Deficiency; D004272:DNA, Mitochondrial / Q000032:analysis; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000172:deficiency*; D004831:Epilepsies, Myoclonic / Q000201:enzymology / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000172:deficiency*; D016660:NAD(P)H Dehydrogenase (Quinone); D009468:Neuromuscular Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D010085:Oxidative Phosphorylation; D010088:Oxidoreductases / Q000172:deficiency*; D011808:Quinone Reductases / Q000172:deficiency*; D013385:Succinate Dehydrogenase / Q000172:deficiency*; D013577:Syndrome
D004272:DNA, Mitochondrial; D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D014450:Electron Transport Complex III