Abstract
We present clinical and laboratory data from 14 cases with an isolated deficiency of the mitochondrial ATP synthase (7-30% of control) caused by nuclear genetic defects. A quantitative decrease of the ATP synthase complex was documented by Blue-Native electrophoresis and Western blotting and was supported by the diminished activity of oligomycin/aurovertin-sensitive ATP hydrolysis in fibroblasts (10 cases), muscle (6 of 7 cases), and liver (one case). All patients had neonatal onset and elevated plasma lactate levels. In 12 patients investigated 3-methyl-glutaconic aciduria was detected. Seven patients died, mostly within the first weeks of life and surviving patients showed psychomotor and various degrees of mental retardation. Eleven patients had hypertrophic cardiomyopathy; other clinical signs included hypotonia, hepatomegaly, facial dysmorphism and microcephaly. This phenotype markedly differs from the severe central nervous system changes of ATP synthase disorders caused by mitochondrial DNA mutations of the ATP6 gene presenting mostly as NARP and MILS.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / metabolism
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Adolescent
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Age of Onset
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Cardiomyopathy, Hypertrophic, Familial / enzymology
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Cardiomyopathy, Hypertrophic, Familial / genetics
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Cardiomyopathy, Hypertrophic, Familial / physiopathology
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Cell Nucleus / genetics
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Child
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Child, Preschool
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Face / abnormalities
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Female
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Genetic Predisposition to Disease / genetics*
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Hepatomegaly / enzymology
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Hepatomegaly / genetics
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Hepatomegaly / physiopathology
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Humans
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Infant
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Infant, Newborn
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Lactic Acid / blood
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Male
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Microcephaly / enzymology
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Microcephaly / genetics
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Mitochondria / enzymology
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Mitochondria / genetics
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Mitochondrial Diseases / enzymology*
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Mitochondrial Diseases / genetics*
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Mitochondrial Diseases / physiopathology
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Mitochondrial Encephalomyopathies / enzymology*
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Mitochondrial Encephalomyopathies / genetics*
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Mitochondrial Encephalomyopathies / physiopathology
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Mitochondrial Proton-Translocating ATPases / deficiency*
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Mitochondrial Proton-Translocating ATPases / genetics
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Syndrome
Substances
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Lactic Acid
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Adenosine Triphosphate
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Mitochondrial Proton-Translocating ATPases