Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth.
OBJECTIVE
Barth Syndrome (BTHS) is an X-linked multisystem disorder (OMIM 302060) usually diagnosed in infancy and characterized by cardiac problems [dilated cardiomyopathy (DCM) ± endocardial fibroelastosis (EFE) ± left ventricular non-compaction (LVNC)], proximal myopathy, feeding problems, growth retardation, neutropenia, organic aciduria and variable respiratory chain abnormalities. We wished to determine whether BTHS had a significant impact on fetal and perinatal health in a large cohort of family groups originating from a defined region.


METHODS
Case note review on 19 families originating from the UK and known to the Barth Syndrome Service of the Bristol Royal Hospital for Children.


RESULTS
Details are presented on six kindreds (32%) with genetically and biochemically proven BTHS that demonstrate a wider phenotype including male fetal loss, stillbirth and severe neonatal illness or death. In these families, 9 males were stillborn and 14 died as neonates or infants but there were no losses of females. BTHS was definitively proven in five males with fetal onset of DCM ± hydrops/EFE/LVNC.


CONCLUSIONS
These findings stress the importance of considering BTHS in the differential diagnosis of unexplained male hydrops, DCM, EFE, LVNC or pregnancy loss, as well as in neonates with hypoglycemia, lactic acidosis and idiopathic mitochondrial disease.
Steward
C G
CG
Department of Paediatric Haematology, Oncology & BMT, Royal Hospital for Children, Upper Maudlin St, Bristol, UK. colin.steward@bristol.ac.uk
Newbury-Ecob
R A
RA
Hastings
R
R
Smithson
S F
SF
Tsai-Goodman
B
B
Quarrell
O W
OW
Kulik
W
W
Wanders
R
R
Pennock
M
M
Williams
M
M
Cresswell
J L
JL
Gonzalez
I L
IL
Brennan
P
P
D000217:Acyltransferases; D056889:Barth Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002308:Cardiolipins / Q000097:blood; D002311:Cardiomyopathy, Dilated / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D041321:Chromosomes, Human, X / Q000235:genetics*; D015331:Cohort Studies; D004695:Endocardial Fibroelastosis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D005260:Female; D005313:Fetal Death / Q000453:epidemiology / Q000235:genetics*; D005315:Fetal Diseases / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D056830:Isolated Noncompaction of the Ventricular Myocardium / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D008246:Lysophospholipids / Q000097:blood; D008297:Male; D010375:Pedigree; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D050497:Stillbirth / Q000453:epidemiology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D006113:United Kingdom / Q000453:epidemiology
D015415:Biomarkers; D002308:Cardiolipins; D008246:Lysophospholipids; D014157:Transcription Factors; C067188:monolysocardiolipin; D000217:Acyltransferases; C108675:TAFAZZIN protein, human
Pediatr Transplant. 2007 May;11(3):327-31
17430492
Am J Med Genet A. 2005 May 1;134(4):409-14
15793838
Prenat Diagn. 1997 Oct;17(10):983-8
9358581
Nat Genet. 1996 Apr;12(4):385-9
8630491
Fertil Steril. 2007 Apr;87(4):976.e5-7
17241629
J Inherit Metab Dis. 1996;19(2):157-60
8739954
J Inherit Metab Dis. 2006 Oct;29(5):684
16906470
Anal Biochem. 2009 Apr 15;387(2):230-7
19454236
Lab Invest. 2005 Jun;85(6):823-30
15806137
Eur J Pediatr. 2008 Aug;167(8):941-4
17846786
J Pediatr. 1991 Nov;119(5):738-47
1719174
Pediatr Cardiol. 2005 Sep-Oct;26(5):632-7
16235007
J Neurol Sci. 1983 Dec;62(1-3):327-55
6142097
Prenat Diagn. 2006 May;26(5):462-5
16548007
Acta Paediatr. 2001 May;90(5):584-6
11430723
Am J Hum Genet. 1997 Oct;61(4):868-72
9382097
Lab Invest. 2007 Jan;87(1):40-8
17043667
J Pediatr. 1999 Sep;135(3):273-6
10484787
Pediatrics. 2006 Aug;118(2):e337-46
16847078
J Lipid Res. 2005 Jun;46(6):1182-95
15805542
Pediatrics. 1979 Jul;64(1):24-9
572031
Mol Genet Metab. 2002 Dec;77(4):319-25
12468278
Biochem Biophys Res Commun. 2000 Dec 20;279(2):378-82
11118295
Circulation. 2001 Mar 6;103(9):1256-63
11238270
Methods Cell Biol. 2007;80:223-40
17445697
Clin Chem. 2008 Feb;54(2):371-8
18070816
Acta Paediatr. 2004 Mar;93(3):419-21
15124852
Clin Dysmorphol. 2009 Oct;18(4):185-7
19648820
J Pediatr. 1999 Sep;135(3):311-5
10484795