New targets for monitoring and therapy in Barth syndrome

W. Reid Thompson, Brittany Decroes, Rebecca Mcclellan, Jessica Rubens, Frédéric M. Vaz, Kara Kristaponis, Dimitrios Avramopoulos, Hilary J. Vernon

Research output: Contribution to journalArticle

Abstract

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1001-1010
Number of pages10
JournalGenetics in Medicine
Volume18
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

Barth Syndrome
Cardiolipins
Genotype
Exercise
Phenotype
Metabolome
Muscle Strength
Echocardiography
Motor Activity
Multivariate Analysis
Acids
Genes

Keywords

  • 3-methylglutaconic acid
  • Barth syndrome
  • cardiolipin
  • cardiomyopathy
  • myopathy

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Thompson, W. R., Decroes, B., Mcclellan, R., Rubens, J., Vaz, F. M., Kristaponis, K., ... Vernon, H. J. (2016). New targets for monitoring and therapy in Barth syndrome. Genetics in Medicine, 18(10), 1001-1010. DOI: 10.1038/gim.2015.204

New targets for monitoring and therapy in Barth syndrome. / Thompson, W. Reid; Decroes, Brittany; Mcclellan, Rebecca; Rubens, Jessica; Vaz, Frédéric M.; Kristaponis, Kara; Avramopoulos, Dimitrios; Vernon, Hilary J.

In: Genetics in Medicine, Vol. 18, No. 10, 01.10.2016, p. 1001-1010.

Research output: Contribution to journalArticle

Thompson, WR, Decroes, B, Mcclellan, R, Rubens, J, Vaz, FM, Kristaponis, K, Avramopoulos, D & Vernon, HJ 2016, 'New targets for monitoring and therapy in Barth syndrome' Genetics in Medicine, vol 18, no. 10, pp. 1001-1010. DOI: 10.1038/gim.2015.204
Thompson WR, Decroes B, Mcclellan R, Rubens J, Vaz FM, Kristaponis K et al. New targets for monitoring and therapy in Barth syndrome. Genetics in Medicine. 2016 Oct 1;18(10):1001-1010. Available from, DOI: 10.1038/gim.2015.204

Thompson, W. Reid; Decroes, Brittany; Mcclellan, Rebecca; Rubens, Jessica; Vaz, Frédéric M.; Kristaponis, Kara; Avramopoulos, Dimitrios; Vernon, Hilary J. / New targets for monitoring and therapy in Barth syndrome.

In: Genetics in Medicine, Vol. 18, No. 10, 01.10.2016, p. 1001-1010.

Research output: Contribution to journalArticle

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