title: New targets for monitoring and therapy in Barth syndrome.
abstract: Barth syndrome (BTHS), an X-linked disorder caused by defects in TAZ, is the only known single-gene disorder of cardiolipin remodeling. We hypothesized that through analysis of affected individuals, we would gain a better understanding of the range of clinical features and identify targets for monitoring and therapy.
  
  
  
  We conducted a multidisciplinary investigation involving 42 patients with BTHS, including echocardiograms, muscle strength testing, functional exercise capacity testing, physical activity assessments, cardiolipin analysis, 3-methylglutaconic acid analysis, and review of genotype data. We analyzed data points to provide a quantitative spectrum of disease characteristics and to identify relationships among phenotype, genotype, and relevant metabolites.
  
  
  
  Echocardiography revealed considerable variability in cardiac features. By contrast, almost all patients had significantly reduced functional exercise capacity. Multivariate analysis revealed significant relationships between cardiolipin ratio and left ventricular mass and between cardiolipin ratio and functional exercise capacity. We additionally identified genotypes associated with a less severe metabolic and clinical profile.
  
  
  
  We defined previously unrecognized metabolite/phenotype/genotype relationships, established targets for therapeutic monitoring, and validated avenues for clinical assessment. In addition to providing insight into BTHS, these studies also provide insight into the myriad of multifactorial disorders that converge on the cardiolipin pathway.Genet Med 18 10, 1001-1010.
authors: Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: W Reid
authors: WR
authors: Thompson
authors: Department of Physical Therapy, Kennedy Krieger Institute, Baltimore, Maryland.
authors: Brittany
authors: 0000-0003-2247-9254
authors: B
authors: DeCroes
authors: Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland.
authors: Rebecca
authors: R
authors: McClellan
authors: Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland.
authors: Jessica
authors: J
authors: Rubens
authors: Department of Clinical Chemistry and Pediatrics, Academic Medical Center, Amsterdam, The Netherlands.
authors: Frédéric M
authors: FM
authors: Vaz
authors: Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland.
authors: Kara
authors: K
authors: Kristaponis
authors: McKusick-Nathans Institute of Genetic Medicine, Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland.
authors: Dimitrios
authors: D
authors: Avramopoulos
authors: Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland.|McKusick-Nathans Institute of Genetic Medicine, Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland.
authors: Hilary J
authors: 0000-0001-9940-9866
authors: HJ
authors: Vernon
mesh_terms: D000217:Acyltransferases; D000293:Adolescent; D000328:Adult; D056889:Barth Syndrome / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D002308:Cardiolipins / Q000097:blood* / Q000235:genetics; D009202:Cardiomyopathies / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D005838:Genotype; D005977:Glutarates / Q000097:blood; D006801:Humans; D008297:Male; D053580:Muscle Strength / Q000235:genetics; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D002308:Cardiolipins; D005977:Glutarates; D014157:Transcription Factors; C022034:3-methylglutaconic acid; D000217:Acyltransferases; C108675:TAFAZZIN protein, human