RT Book, Section
A1 Dimauro, Salvatore
A2 Rudolph, Colin D.
A2 Rudolph, Abraham M.
A2 Lister, George E.
A2 First, Lewis R.
A2 Gershon, Anne A.
SR Print(0)
ID 6726441
T1 Chapter 158. Respiratory Chain Disorders
T2 Rudolph's Pediatrics, 22e
YR 2011
FD 2011
PB The McGraw-Hill Companies
PP New York, NY
SN 978-0-07-149723-7
LK accesspediatrics.mhmedical.com/content.aspx?aid=6726441
RD 2024/04/19
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  integenomic  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  159).