TY - CHAP M1 - Book, Section TI - Respiratory Chain Disorders A1 - Pascual, Juan M. A1 - DiMauro, Salvatore A2 - Kline, Mark W. Y1 - 2018 N1 - T2 - Rudolph's Pediatrics, 23e AB - The respiratory chain (RC) is the terminal pathway of mitochondrial metabolism, where most energy is produced as adenosine triphosphate (ATP). It is also the only metabolic pathway under dual genetic control: Of the approximately 80 subunits of the RC, 13 are encoded by mitochondrial DNA (mtDNA) and the rest by nuclear DNA (nDNA). Defects of the RC cause an extremely heterogeneous group of disorders that affect both children and adults, often involving multiple tissues and resulting in characteristic syndromes but sometimes affecting single tissues. Disorders due to mutations in mtDNA are especially challenging for the clinician because the rules of mitochondrial genetics make for intrafamilial variability, including often elusive maternal inheritance, syndromic or nonsyndromic multisystem involvement, and variably severe laboratory abnormalities. Disorders due to mutations in nDNA are inherited as Mendelian traits and include “direct hits,” or mutations directly affecting subunits of the RC; “indirect hits,” or mutations in proteins needed for the proper assembly of individual RC complexes; and defects of intergenomic signaling, such as mutations in proteins needed for the maintenance of mtDNA (translation, replication, repair). The central disorder of pediatric interest is Leigh syndrome (LS), which reflects the consequences of impaired energy metabolism on the developing brain and is characterized clinically by psychomotor regression and signs of brain stem dysfunction; radiologically, it is characterized by bilateral, symmetrical lesions in the basal ganglia and the brain stem. LS is associated with both mtDNA- and nDNA-related disorders and with defects of pyruvate metabolism (see Chapter 154). SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/11/07 UR - accesspediatrics.mhmedical.com/content.aspx?aid=1182929411 ER -