Genetic disorders of mitochondria cause disease when they reduce subcellular energy production through a variety of impairments in the electron transport chain, thus decreasing oxidative phosphorylation. Such abnormalities typically lead to neuropathies and/or myopathies including cardiomyopathies. Hepatic and renal pathology may also occur. The age of onset and severity are variable, but signs and symptoms are often present during infancy. The metabolic hallmarks include lactic acidosis, an increased ratio of blood lactate to pyruvate, and ketonemia. Muscle biopsies show characteristic ragged red fibers, which are obvious with trichrome staining. Some disorders which are inherited through the mother, source of all mitochondrial DNA, lead to early blindness due to progressive optic neuropathy, i.e., Leber's Hereditary Optic Neuropathy. Exciting recent research with gene replacement therapy and stem cell technology has provided new insights and hope for patients with genetic blindness. Other disorders affecting mitochondrial DNA mutations may also eventually be treated with molecular (gene replacement) or advanced cellular (stem cell) therapeutic strategies. In addition, early diagnosis through newborn screening is now routinely achieved for some disorders such as biotinidase deficiency, allowing curative therapy through nutritional supplements.
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