ABSTRACT
A diagnosis of mitochondrial DNA depletion may be suspected on the basis of fasting hypoglycemia and liver dysfunction characterized by elevations of gamma glutamyl transferase, often greater than alanine aminotransferase and aspartate aminotransferase, or by elevated creatine phosphokinase and ragged red fibers. Acquired mitochondrial DNA depletion syndromes have been described in adults as a complication of the treatment of HIV-1 and hepatitis B virus infections with the reverse transcriptase inhibitors azidothymidine and fluoriodoarauracil. Assay of purified mitochondria from skeletal muscle and liver revealed a complete absence of activity of mitochondrial DNA polymerase γ. Human DNA polymerase γ has been characterized as a reverse transcriptase. The cloning of the human mitochondrial DNA polymerase has facilitated molecular dissection. Avoidance of fasting is an important element in management of the hepatic forms of mitochondrial DNA depletion. Treatment of the nonhepatic forms of mitochondrial DNA depletion also includes carnitine and cofactor therapy.
