Deficiency of mitochondrial ATP synthase of nuclear genetic origin.

• 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.

Nyckelord

Adenosine Triphosphate

metabolism

Adolescent

Age of Onset

Cardiomyopathy

Hypertrophic

Familial

enzymology

genetics

physiopathology

Cell Nucleus

genetics

Child

Child

Preschool

Face

abnormalities

Female

Genetic Predisposition to Disease

genetics

Hepatomegaly

enzymology

genetics

physiopathology

Humans

Infant

Infant

Newborn

Lactic Acid

blood

Male

Microcephaly

enzymology

genetics

Mitochondria

enzymology

genetics

Mitochondrial Diseases

enzymology

genetics

physiopathology

Mitochondrial Encephalomyopathies

enzymology

genetics

physiopathology

Mitochondrial Proton-Translocating ATPases

deficiency

genetics

Syndrome

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)