RT Book, Section
A1 Longo, Nicola
A1 Pasquali, Marzia
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102703505
T1 Primary Carnitine Deficiency
T2 Clinical Genomics: Practical Applications in Adult Patient Care
YR 2014
FD 2014
PB McGraw-Hill Education
PP New York, NY
SN 9780071622448
LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102703505
RD 2024/04/19
AB Disease  summary:Primary  carnitine  deficiency  (OMIM  212140)  is  a  disorder  of  the  carnitine  cycle  that  impairs  fatty  acid  oxidation.  It  is  caused  by  mutations  in  the  SLC22A5  gene  encoding  the  OCTN2  carnitine  transporter.  Primary  carnitine  deficiency  has  a  frequency  of  about  1:40,000,  with  1%  of  the  population  being  carrier  for  this  condition.  It  has  a  very  high  frequency  in  the  Faroe  Islands  (prevalence  1:1300  people,  incidence  1:720)  due  to  a  founder  effect.The  lack  of  the  plasma  membrane  carnitine  transporter  results  in  urinary  carnitine  wasting,  low  serum  carnitine  levels  (0-5  μM,  normal  25-50  μM),  and  decreased  intracellular  carnitine  accumulation.  Affected  patients  can  have  a  predominant  metabolic  (hypoglycemia,  hepatic  encephalopathy)  or  cardiac  (cardiomyopathy,  arrhythmia)  presentation.  Some  people  remain  asymptomatic  for  long  time,  but  are  at  risk  for  sudden  cardiac  death.Hereditary  basis:Primary  carnitine  deficiency  is  transmitted  as  an  autosomal  recessive  disorder  caused  by  mutations  in  the  SLC22A5  gene  on  5q31.1.  Penetrance  in  affected  individuals  is  thought  to  be  very  high,  although  quite  a  few  people  are  identified  as  adults  due  to  expanded  newborn  screening.Differential  diagnosis:Primary  carnitine  deficiency  needs  to  be  differentiated  from  secondary  carnitine  deficiency.  This  can  occur  in  disorders  of  the  carnitine  cycle  (carnitine-acylcarnitine  translocase  [CACT]  or  carnitine  palmitoyl  transferase  2  [CPT-2]  deficiency)  and  fatty  acid  oxidation  (MCAD,  VLCAD,  LCHAD,  TFP  deficiency),  organic  acidemias  (propionic,  methylmalonic,  isovaleric,  and  glutaric  acidemia,  3-methylcrotonylglycinuria,  multiple  carboxylase  deficiency,  and  other  more  rare),  renal  disease  (renal  Fanconi  syndrome,  chronic  renal  failure,  dialysis),  lysinuric  protein  intolerance  (LPI),  chronic  ketosis  or  ketogenic  diet,  extreme  prematurity,  prolonged  use  of  intravenous  nutrition  not  supplemented  by  carnitine,  and  drug  therapy  (valproic  acid,  phenobarbital,  phenytoin,  carbamazepine,  drugs  containing  pivalic  acid).