Mitochondrial function is carried out by proteins that are coded for by both nuclear and mitochondrial genes. These enzymes are extremely complicated, and several are quite large. The mitochondrial genome encodes 13 subunits of the enzymes involved in mitochondrial oxidative phosphorylation. More than 85 autosomal genes code for the rest of the subunits of these enzymes. In children, only about 15% of cases of mitochondrial disease are caused by mutations in mitochondrial DNA (mtDNA); the rest are due to mutations in nuclear genes. The most frequent cases in several large series have been mutations that lead to a reduction in the ability of the mtDNA to maintain itself. Large population studies show carrier rates of about 2% of the population for mutations in polymerase (DNA directed), gamma (POLG), and deoxyguanosine kinase (DGUOK). Most disorders show autosomal recessive inheritance. A few are X linked or passed on by maternal mtDNA mutations, such as mitochondrial encephalopathy with lactic acidosis (MELAS) and mitochondrial encephalopathy with ragged red fibers (MERRF), or deletions such as maternally inherited diabetes and deafness (MIDD).
Repairing the basic energy deficit and getting the appropriate drugs and cofactors to the appropriate location within the mitochondrion are difficult. Nevertheless, a number of strategies are used, including judicious physical therapy and exercise with adequate rest, adequate nutrition, and cofactors for the deficient pathway. Specific treatment is limited for most mitochondrial defects. Vitamin cofactors for the respiratory chain, such as riboflavin and pharmaceutical forms of coenzyme Q, are often used. When a single organ bears most of the damage, organ transplant may be effective. Identification of family members at risk may allow earlier diagnosis and treatment.
The author would like to acknowledge Dr. Margretta R. Seashore for her superb work in the last edition. Hers was an excellent analysis of the topic and has informed much of the present discussion.
de Baulny HO, Benoist JF, Rigal O, et al: Methylmalonic and propionic acidaemias: management and outcome, J Inherit Metab Dis 28(3):415–423,
Heese BA: Current strategies in the management of lysosomal storage dis eases, Semin Pediatr Neurol 15(3):119–126, 2008
Kayser MA: Inherited metabolic diseases in neurodevelopmental and neuro behavioral disorders, Semin Pediatr Neurol 15(3):127–131, 2008
Kliegman RM, Stanton BF, St. Geme JW, et al: Nelson Textbook of Pediatrics, ed 19, Philadelphia, 2011, Elsevier Science
Koeberl DD, Kishnani PS, Chen YT: Glycogen storage disease types I and II: treatment updates, J Inherit Metab Dis 30(2):159–164, 2007
Kompare M, Rizzo WB: Mitochondrial fatty-acid oxidation disorders, Semin
Pediatr Neurol 15(3):140–149, 2008
Tuchman M, Lee B, Lichter-Konecki U, et al: Cross-sectional multicenter study of patients with urea cycle disorders in the United States, Mol Genet
Metab 94(4):397–402, 2008
Clarence W. Gowen, Jr.
ASSESSMENT OF THE MOTHER, FETUS, AND NEWBORN