Pediatric Cardiology

, Volume 26, Issue 5, pp 632–637 | Cite as

Ventricular Arrhythmia in the X-linked Cardiomyopathy Barth Syndrome

  • C.T. Spencer
  • B.J. Byrne
  • M.H. Gewitz
  • S.B. Wechsler
  • A.C. Kao
  • E.P. Gerstenfeld
  • A.D. Merliss
  • M.P. Carboni
  • R.M. Bryant


Barth syndrome is an X-linked disorder characterized by dilated cardiomyopathy, cyclic neutropenia, skeletal myopathy, abnormal mitochondria, and growth deficiency. The primary defect is a mutation in the TAZ gene on the X chromosome at Xq28, resulting in abnormal phospholipid biosynthesis and cardiolipin deficiency. To date, there has been no systematic evaluation of the cardiac phenotype. We report five cases of cardiac arrest and/or placement of an internal cardiac defibrillator with documented ventricular arrhythmia. We suggest that ventricular arrhythmia is part of the primary phenotype of the disorder and that patients should be screened accordingly.


Cardiomyopathy Arrhythmia Barth syndrome 



We thank Iris Gonzalez, Ph.D., for the mutation analysis. We are also grateful to the families of these patients for their willingness to contribute. C.T.S. is a recipient of the Howard Hughes Medical Institutes Award for faculty development.


  1. 1.
    Barth, PG, Scholte, HR, Berden, JA,  et al. 1983An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytesJ Neurol Sci62327355PubMedCrossRefGoogle Scholar
  2. 2.
    Barth, PG, Wanders, RJ, Vreken, P,  et al. 1999X-linked cardioskeletal myopathy and neutropenia (Barth syndrome) (MIM 302060)J Inherit Metab Dis22555567PubMedCrossRefGoogle Scholar
  3. 3.
    Bione, S, D’Adamo, P, Maestrini, E,  et al. 1996A novel X-linked gene, G4.5. is responsible for Barth syndromeNat Genet12385389PubMedCrossRefGoogle Scholar
  4. 4.
    Bolhuis, PA, Hensels, GW, Hulsebos, TJ, Baas, F, Barth, PG 1991Mapping of the locus for X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria (Barth syndrome) to Xq28Am J Hum Genet48481485PubMedGoogle Scholar
  5. 5.
    D’Adamo, P, Fassone, L, Gedeon, A,  et al. 1997The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathiesAm J Hum Genet61862867PubMedGoogle Scholar
  6. 6.
    Doval, HC, Nul, DR, Grancelli, HO,  et al. 1996Nonsustained ventricular tachycardia in severe heart failure: independent marker of increased mortality due to sudden death. GESICA–GEMA investigatorsCirculation9431983203PubMedGoogle Scholar
  7. 7.
    Fauchier, L, Babuty, D, Cosnay, P,  et al. 2000Long-term prognostic value of time domain analysis of signal-averaged electrocardiography in idiopathic dilated cardiomyopathyAm J Cardiol85618623PubMedCrossRefGoogle Scholar
  8. 8.
    Grimm, W, Christ, M, Bach, J, Muller, HH, Maisch, B 2003Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy StudyCirculation10828832891PubMedCrossRefGoogle Scholar
  9. 9.
    Hohnloser, SH, Klingenheben, T, Bloomfield, D, Dabbous, O, Cohen, RJ 2003Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational studyJ Am Coll Cardiol4122202224PubMedCrossRefGoogle Scholar
  10. 10.
    Johnston, J, Kelley, RI, Feigenbaum, A,  et al. 1997Mutation characterization and genotype–phenotype correlation in Barth syndromeAm J Hum Genet6110531058PubMedCrossRefGoogle Scholar
  11. 11.
    La Rovere, MT, Pinna, GD, Maestri, R,  et al. 2003Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart failure patientsCirculation107565570PubMedCrossRefGoogle Scholar
  12. 12.
    Liu, Y, Sato, T, O’Rourke, B, Marban, E 1998(1998) Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection?Circulation9724632469PubMedGoogle Scholar
  13. 13.
    McMillin, JB, Dowhan, W 2002Cardiolipin and apoptosisBioohim Biophys Acta158597107Google Scholar
  14. 14.
    Nerheim, P, Krishnan, SC, Olshansky, B, Shivkumar, K 2001Apoptosis in the genesis of cardiac rhythm disordersCardiol Clin19155163PubMedCrossRefGoogle Scholar
  15. 15.
    Neustein, HB, Lurie, PR, Dahms, B, Takahashi, M 1979An X-linked recessive cardiomyopathy with abnormal mitochondriaPediatrics642429PubMedGoogle Scholar
  16. 16.
    Neustein, HB, Lurie, PR, Fugita, M 1979Endocardial fibroelastosis found on transvascular endomyocardial biopsy in childrenArch Pathol Lab Med103214219PubMedGoogle Scholar
  17. 17.
    Neuwald, AF 1997Barth syndrome may be due to an acyltransferase deficiencyCurr Biol7R465R466PubMedCrossRefGoogle Scholar
  18. 18.
    Schlame, M, Towbin, JA, Heerdt, PM,  et al. 2002Deficiency of tetralinoleoyl–cardiolipin in Barth syndromeAnn Neurol51634637PubMedCrossRefGoogle Scholar
  19. 19.
    Vreken, P, Valianpour, F, Nijtmans, LG,  et al. 2000Defective remodeling of cardiolipin and phosphatidylglycerol in Barth syndromeBiochem Biophys Res Commun279378382PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • C.T. Spencer
    • 1
  • B.J. Byrne
    • 1
  • M.H. Gewitz
    • 2
  • S.B. Wechsler
    • 3
  • A.C. Kao
    • 4
  • E.P. Gerstenfeld
    • 4
  • A.D. Merliss
    • 5
  • M.P. Carboni
    • 6
  • R.M. Bryant
    • 1
  1. 1.Department of Pediatrics, Division of CardiologyUniversity of FloridaGainesvilleUSA
  2. 2.Department of Pediatrics, Division of CardiologyNew York Medical CollegeValhallaUSA
  3. 3.Department of Pediatrics, Division of CardiologyUniversity of MichiganAnn ArborUSA
  4. 4.Cardiovascular DivisionUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Bryan LGH Heart InstituteLincolnUSA
  6. 6.Department of PediatricsDivision of CardiologyDuke University Medical CenterDurhamUSA

Personalised recommendations