TY  - CHAP
M1  - Book, Section
TI  - Medium-chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
A1  - Bissonnette, Bruno
A1  - Luginbuehl, Igor
A1  - Engelhardt, Thomas
PY  - 2019
T2  - Syndromes: Rapid Recognition and Perioperative Implications, 2e
AB  - This  inherited  metabolic  disorder  is  the  most  common  form  of  Acyl-CoA  dehydrogenase  deficiencies.  In  the  USA,  it  affects  approximately  1  in  15,000  to  20,000  newborns  of  both  genders  equally,  but  the  incidence  is  even  higher  in  people  from  Northern  Europe  (up  to  1  in  12,000  newborns).  Inheritance  is  autosomal  recessive  and  the  defect  in  the  Acyl-CoA  dehydrogenase,  C-4  to  C-12  straight  chain  (ACADM)  gene  has  been  mapped  to  chromosome  1p31.1.  Medium-chain  fatty  acids  consist  of  aliphatic  tails  of  6  to  12  carbon  atoms,  and  MCAD  has  a  chain-length  substrate  specificity  ranging  from  C4  to  C12.  About  80%  of  patients  are  homozygous  for  a  single  mutation  while  the  remaining  20%  are  either  single  mutation  carriers  or  compound  heterozygotes.  In  many  countries,  standard  neonatal  screening  now  includes  testing  for  MCADD,  which  then  allows  for  proactive  treatment  during  times  of  decreased  fluid  and  caloric  intake  and/or  increased  energy  demands  and  allows  for  favorable  prognosis.  Onset  is  usually  in  the  first  2  years  of  life  (typically  between  3  and  15  months  of  age).  However,  in  some  rare  cases,  symptoms  may  not  become  apparent  until  later  in  childhood  or  even  adulthood.  An  episode  of  decompensation  is  usually  triggered  by  prolonged  fasting  and/or  increased  energy  demands,  such  as  during  a  minor  illness  (eg,  gastrointestinal  infection  with  vomiting/diarrhea),  surgery,  or  any  other  forms  of  stress.  Metabolic  decompensation  is  more  likely  the  younger  the  patient  is  (less  reserves,  higher  metabolic  rate)  and  happens  once  the  hepatic  glycogen  supplies  become  depleted.  In  healthy  people,  fatty  acids  are  metabolized  to  ketones,  which  then  become  a  major  energy  source  after  the  glycogen  stores  have  been  exhausted.  However,  MCADD  results  in  accumulation  of  fatty  acids  and  inadequate  supply  of  ketones  (such  as  ketone  beta-hydroxybutyrate)  and  eventually  severe  hypoglycemia.  Nevertheless,  the  presence  of  ketones  does  not  eliminate  the  diagnosis  of  MCADD,  since  29%  of  patients  subsequently  diagnosed  with  the  disorder  had  ketones  in  their  urine  at  the  time  of  clinical  onset.  The  accumulation  of  medium-chain  organic  acids,  corresponding  acyl-carnitines  and  acyl-CoAs—the  biochemical  hallmark  of  beta-oxidation  defects—can  lead  to  toxic  effects  on  liver,  muscles,  and  central  nervous  system.  Metabolic  decompensation  has  a  mortality  rate  of  up  to  25%,  and  survivors  carry  a  significant  risk  of  long-term  illness  and  developmental  disability.  The  initial  signs  of  metabolic  decompensation  include  lethargy  (in  84%  of  patients),  vomiting  (in  66%),  encephalopathy  (in  49%),  respiratory  arrest  (in  48%),  seizures  (in  43%),  cardiac  arrest  (in  36%),  and  even  sudden  death  (in  18%).  Additional  findings  include  severe  metabolic  acidosis,  hypoketotic  hypoglycemia  (not  an  early  sign!),  hyperammonemia,  arrhythmias,  muscle  weakness  and  coma.  Acute  liver  failure  may  present  with  hepatomegaly  (in  44%  of  patients,  secondary  to  accumulation  of  fat),  pathologic  liver  function  tests  (often  normal  partial  thromboplastin  time  and  only  mildly  prolonged  prothrombin  time  and  elevated  serum  transaminases  levels),  and  encephalopathy  (secondary  to  hyperammonemia  and  accumulation  of  other  toxic  metabolites).  Some  of  these  patients  were  labeled  as  sudden  infant  death  syndrome  before  autopsy  revealed  MCADD.  Cardiac  anomalies  have  been  described  in  some  MCADD  patients  and  include  cardiomyopathy  (fatty  myocardium  in  39%  of  autopsies;  unspecified  cardiomyopathy  in  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - accessanesthesiology.mhmedical.com/content.aspx?aid=1164060613
ER  -