TY  - CHAP
M1  - Book, Section
TI  - Barth Syndrome: A Disorder of Cardiolipin Remodeling
A1  - Vernon, Hilary
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
PY  - 2019
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Barth  syndrome,  also  known  as  3-methylglutaconic  aciduria  type  II,  is  a  rare  X-linked  disorder  caused  by  defective  activity  of  tafazzin,  leading  to  abnormal  cardiolipin  remodeling  and  an  abnormal  composition  of  cardiolipin  species  in  the  inner  mitochondrial  membrane.Cardiolipin  is  a  phospholipid  composed  of  two  phosphatidyl  groups  linked  to  a  glycerol  backbone  and  four  fatty  acyl  chains,  synthesized  in  a  several-step  pathway.  Cardiolipin  is  found  primarily  in  the  inner  mitochondrial  membrane  and  at  contact  sites  between  the  inner  and  outer  mitochondrial  membrane.Many  physiologic  functions  have  been  assigned  to  cardiolipin  including  roles  in  maintaining  mitochondrial  structure,  organizing  mitochondrial  supercomplexes,  and  in  apoptosis.  Cardiolipin  has  also  been  implicated  in  multiple  disease  processes  including  diabetes  and  obesity.  The  only  known  Mendelian  disease  associated  with  an  abnormality  in  cardiolipin  transacylation  is  Barth  syndrome.Major  clinical  features  in  Barth  syndrome  include  cardiomyopathy,  neutropenia,  and  skeletal,  muscle,  and  growth  abnormalities.  Both  the  cardiomyopathy  and  neutropenia  have  an  unpredictable  waxing  and  waning  severity  throughout  an  individual’s  lifetime.Biochemical  findings  commonly  found  in  individuals  with  Barth  syndrome  include:  urine  organic  acids  with  increased  3-methylglutaconic  acid,  3-methylglutaric  acid,  and  2-ethylhydracrylic  acid,  elevated  plasma  3-methylglutaconic  acid,  and  abnormal  cardiolipin  composition  including  decreased  tetralinoleyl-cardiolipin  and  increased  monolysocardiolipin  in  a  variety  of  tissues.  Other  laboratory  abnormalities  include  intermittent  lactic  acidemia,  relatively  reduced  plasma  arginine  and  elevated  plasma  proline,  hypocholesterolemia,  hypoglycemia,  mild  elevations  in  plasma  creatine  kinase,  and  reduced  prealbumin.  Female  heterozygotes  do  not  have  detectable  biochemical  abnormalities.Tafazzin  (TAZ)  is  encoded  by  TAZ,  an  11  exon  gene  located  at  Xq28.  Mutations  in  TAZ  found  in  affected  males  include:  small  insertions  or  deletions  (16%),  nonsense  mutations  (14%),  missense  mutations  (48%),  splicing  (15%),  and  large  exonic  deletions  (7%).  No  genotype-phenotype  correlation  has  been  observed,  and  penetrance  is  believed  to  be  complete,  with  variable  expressivity.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/20
UR  - ommbid.mhmedical.com/content.aspx?aid=1181440017
ER  -