title: Diseases of adenosine triphosphate synthesis in children.
abstract: There is an expanding understanding of primary genetic oxidative-phosphorylation disorders and the recognition of new multi-system clinical phenotypes in the energy metabolism diseases. Although initially recognized in association with mitochondrial DNA mutations, there is progress in the more laborious identification of nuclear DNA encoded genes relevant to mitochondrial structure and function. More pathogenic mitochondrial DNA and nuclear DNA mutations have been identified. Diagnosis of these disorders is often difficult and relies on a concurrence of findings, including recognition of a variety of clinical signs and symptoms, biochemical marker screening, electron transport chain enzyme measurements, and mitochondrial DNA or nuclear DNA mutation assay of genes relevant to mitochondrial structure, function or adenosine triphosphate metabolic pathways. Clinical diagnostic assessment now can be augmented by physiologic imaging techniques, including nuclear magnetic resonance spectroscopy and positron emission tomography. These capabilities should be increasingly helpful for studies of clinical progression and therapeutic intervention. Biologic studies, in families and patients, are beginning to address the factors of mitochondrial replication and segregation that underlie cellular/tissue heteroplasmy and clinical variability. Most epigenetic factors affecting organ-specific and phenotypic variability, however, remain to be elaborated.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, 02129, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Sims
authors.forename: David
authors.initials: D
authors.lastname: Holtzman
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D002648:Child; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004579:Electron Transport; D006801:Humans; D008659:Metabolic Diseases / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D009154:Mutation
chemical_list: D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate; D004247:DNA