title: Natural history of Barth syndrome: a national cohort study of 22 patients.
abstract: BACKGROUND
  This study describes the natural history of Barth syndrome (BTHS).
  
  
  METHODS
  The medical records of all patients with BTHS living in France were identified in multiple sources and reviewed.
  
  
  RESULTS
  We identified 16 BTHS pedigrees that included 22 patients. TAZ mutations were observed in 15 pedigrees. The estimated incidence of BTHS was 1.5 cases per million births (95%CI: 0.2-2.3). The median age at presentation was 3.1 weeks (range, 0-1.4 years), and the median age at last follow-up was 4.75 years (range, 3-15 years). Eleven patients died at a median age of 5.1 months; 9 deaths were related to cardiomyopathy and 2 to sepsis. The 5-year survival rate was 51%, and no deaths were observed in patients ≥3 years. Fourteen patients presented with cardiomyopathy, and cardiomyopathy was documented in 20 during follow-up. Left ventricular systolic function was very poor during the first year of life and tended to normalize over time. Nineteen patients had neutropenia. Metabolic investigations revealed inconstant moderate 3-methylglutaconic aciduria and plasma arginine levels that were reduced or in the low-normal range. Survival correlated with two prognostic factors: severe neutropenia at diagnosis (<0.5 × 109/L) and birth year. Specifically, the survival rate was 70% for patients born after 2000 and 20% for those born before 2000.
  
  
  CONCLUSIONS
  This survey found that BTHS outcome was affected by cardiac events and by a risk of infection that was related to neutropenia. Modern management of heart failure and prevention of infection in infancy may improve the survival of patients with BTHS without the need for heart transplantation.
authors: AP-HP, Registre français des neutropénies chroniques sévères, Centre de référence des déficits Immunitaires Héréditaires, Service d'Hémato-oncologie Pédiatrique Hôpital Trousseau, Paris, France. cha.rigaud@hotmail.fr
authors: Charlotte
authors: C
authors: Rigaud
authors: Anne-Sophie
authors: AS
authors: Lebre
authors: Renaud
authors: R
authors: Touraine
authors: Blandine
authors: B
authors: Beaupain
authors: Chris
authors: C
authors: Ottolenghi
authors: Allel
authors: A
authors: Chabli
authors: Helene
authors: H
authors: Ansquer
authors: Hulya
authors: H
authors: Ozsahin
authors: Sylvie
authors: S
authors: Di Filippo
authors: Pascale
authors: P
authors: De Lonlay
authors: Betina
authors: B
authors: Borm
authors: Francois
authors: F
authors: Rivier
authors: Marie-Catherine
authors: MC
authors: Vaillant
authors: Michèle
authors: M
authors: Mathieu-Dramard
authors: Alice
authors: A
authors: Goldenberg
authors: Géraldine
authors: G
authors: Viot
authors: Philippe
authors: P
authors: Charron
authors: Marlene
authors: M
authors: Rio
authors: Damien
authors: D
authors: Bonnet
authors: Jean
authors: J
authors: Donadieu
mesh_terms: D000217:Acyltransferases; D000293:Adolescent; D056889:Barth Syndrome / Q000150:complications / Q000235:genetics / Q000401:mortality* / Q000503:physiopathology*; D009202:Cardiomyopathies / Q000150:complications; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D009154:Mutation; D009503:Neutropenia / Q000150:complications; D010375:Pedigree; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics
chemical_list: D014157:Transcription Factors; D000217:Acyltransferases; C108675:TAFAZZIN protein, human
references: Anal Biochem. 2009 Apr 15;387(2):230-7
references: 19454236
references: Pediatrics. 2004 Oct;114(4):925-31
references: 15466086
references: Mol Genet Metab. 2012 May;106(1):115-20
references: 22410210
references: Pediatr Cardiol. 2012 Dec;33(8):1430-4
references: 22427193
references: J Hum Genet. 2002;47(5):229-31
references: 12032589
references: Am J Med Genet. 1994 Apr 15;50(3):255-64
references: 8042670
references: Orphanet J Rare Dis. 2013 Feb 12;8:23
references: 23398819
references: Pediatr Transplant. 2007 May;11(3):327-31
references: 17430492
references: J Pediatr. 1991 Nov;119(5):738-47
references: 1719174
references: Eur J Pediatr. 2011 Nov;170(11):1365-7
references: 21947198
references: Pediatr Cardiol. 2005 Sep-Oct;26(5):632-7
references: 16235007
references: J Neurol Sci. 1983 Dec;62(1-3):327-55
references: 6142097
references: Prenat Diagn. 2006 May;26(5):462-5
references: 16548007
references: Am J Hum Genet. 1997 Oct;61(4):868-72
references: 9382097
references: Am J Hum Genet. 1998 Nov;63(5):1457-63
references: 9792874
references: J Pediatr. 1999 Sep;135(3):273-6
references: 10484787
references: Pediatrics. 2006 Aug;118(2):e337-46
references: 16847078
references: Pediatr Cardiol. 1987;8(1):27-33
references: 3601734
references: Am J Med Genet A. 2004 May 1;126A(4):349-54
references: 15098233
references: Am J Med Genet A. 2012 Nov;158A(11):2726-32
references: 23045169
references: Mol Genet Metab. 2010 Jun;100(2):198-203
references: 20303308
references: Biochem Biophys Res Commun. 2000 Dec 20;279(2):378-82
references: 11118295
references: Pediatr Cardiol. 1997 Mar-Apr;18(2):143-5
references: 9049131
references: Nat Genet. 1996 Apr;12(4):385-9
references: 8630491
references: Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H2122-9
references: 21873497
references: Blood. 2004 Jun 1;103(11):4119-25
references: 14962902
references: Acta Paediatr. 2004 Mar;93(3):419-21
references: 15124852
references: Rev Esp Cardiol (Engl Ed). 2013 Jan;66(1):68-70
references: 22999963
references: Clin Nutr. 2008 Aug;27(4):489-96
references: 18640748
references: J Med Genet. 1995 May;32(5):383-8
references: 7616547
references: Am J Med Genet. 1993 Feb 1;45(3):327-34
references: 8434619
references: Mol Genet Metab. 2003 Dec;80(4):408-11
references: 14654353
references: Orphanet J Rare Dis. 2011 May 19;6:26
references: 21595885
references: Pediatr Phys Ther. 2001 Winter;13(4):175-81
references: 17053636
references: Prenat Diagn. 2010 Oct;30(10):970-6
references: 20812380
references: Am J Hum Genet. 1991 Mar;48(3):481-5
references: 1998334
references: Am J Hum Genet. 1997 Nov;61(5):1053-8
references: 9345098
references: Prog Lipid Res. 2006 Mar;45(2):91-101
references: 16442164
references: Clin Dysmorphol. 2009 Oct;18(4):185-7
references: 19648820
references: J Inherit Metab Dis. 2013 Jan;36(1):91-101
references: 22580961
references: J Pediatr. 1999 Sep;135(3):311-5
references: 10484795