title: Barth syndrome in a female patient.
abstract: BACKGROUND
  Barth syndrome (BTHS) is an X-linked recessive disorder characterized by cardiomyopathy, skeletal myopathy and cyclic neutropenia in male patients. It is caused by mutations in the TAZ gene coding for the tafazzin, a protein involved in the remodeling of cardiolipin. Loss of cardiolipin in the inner mitochondrial membrane results in respiratory chain dysfunction. No specific symptom has been identified in female carriers.
  
  
  METHODS
  We report the first case of BTHS confirmed by TAZ gene analysis in a female patient. This girl experienced severe heart failure at 1-month of age. Echocardiography diagnosed dilated-hypokinetic and hypertrophic cardiomyopathy with noncompaction of the left ventricle. Initial metabolic screening was normal, except for a cyclic neutropenia. Respiratory chain analysis performed on skin fibroblasts revealed a decreased activity of complexes I, III and IV. Screening on a bloodspot showed abnormal monolysocardiolipin:cardiolipin ratio, later confirmed on cultured fibroblasts, indicative of BTHS. Genetic analyses finally confirmed the diagnosis of BTHS, by showing a large intragenic deletion of exons 1 through 5 in the TAZ gene. Cytogenetic analysis showed mosaicism for monosomy X and for a ring X chromosome with a large deletion of the long arm including the Xq28 region. The girl presented recurrent episodes of severe acute heart failure, progressive muscle weakness, and had a fatal septic shock at 3 years.
  
  
  CONCLUSIONS
  This case highlights that the diagnosis of BTHS should also be suspected in female patients presenting a phenotype similar to affected boys. In these cases, analysis of the monolysocardiolipin:cardiolipin ratio in bloodspots is a rapid and sensitive screening tool for BTHS. However clinical expression in a carrier female requires hemizygosity for the mutated allele of the TAZ gene, which supposes a rearrangement of the TAZ gene region on the other X chromosome.
authors.affiliation: Service de Médecine Pédiatrique, CHRU de Tours, Université François Rabelais, Tours, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Cosson
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.forename: Gilles
authors.initials: G
authors.lastname: Simard
authors.forename: Willem
authors.initials: W
authors.lastname: Kulik
authors.forename: Gabor
authors.initials: G
authors.lastname: Matyas
authors.forename: Agnès
authors.initials: A
authors.lastname: Guichet
authors.forename: Hélène
authors.initials: H
authors.lastname: Blasco
authors.forename: Zoha
authors.initials: Z
authors.lastname: Maakaroun-Vermesse
authors.forename: Marie-Catherine
authors.initials: MC
authors.lastname: Vaillant
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Caignec
authors.forename: Alain
authors.initials: A
authors.lastname: Chantepie
authors.forename: François
authors.initials: F
authors.lastname: Labarthe
mesh_terms: D000217:Acyltransferases; D056889:Barth Syndrome / Q000235:genetics / Q000473:pathology*; D002308:Cardiolipins / Q000235:genetics / Q000378:metabolism; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002308:Cardiolipins; D014157:Transcription Factors; D000217:Acyltransferases; C108675:TAFAZZIN protein, human