Skip to main content

Advertisement

SpringerLink
Log in

Eponym

Barth syndrome

  • Review
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Barth syndrome (OMIM #302060) (BTHS) is an X-linked disorder of lipid metabolism characterized by skeletal myopathy, neutropenia, growth delay, and cardiomyopathy. It is caused by mutations in the tafazzin gene (TAZ), which lead to decreased production of an enzyme required to produce cardiolipin, a component of the inner mitochondrial membrane necessary for proper functioning of the electron transport chain. The most common initial presentation of BTHS is significant heart failure due to cardiomyopathy, which is the main cause of death in infancy or childhood. On the other hand, some patients have limited clinical features of BTHS. These patients may be overlooked or misdiagnosed with unclassified congenital myopathy, especially when heart failure is not clinically significant. However, these patients could also develop significant heart failure or life-threatening arrhythmias during or even after childhood. Heart failure in BTHS is often responsive to standard medical therapy, indicating early diagnosis is critical. Diagnostic clues of BTHS in the subclinical stage of heart failure include family histories, findings of lipid storage myopathy in the skeletal muscle biopsy, and elevated plasma brain natriuretic peptide levels. The genetic analysis of TAZ is the only confirmatory method for the diagnosis of BTHS. Conclusion: physicians should be aware of the possibility of this disease and carry out genetic studies when it is considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ades LC, Gedeon AK, Wilson MJ et al (1993) Barth syndrome: clinical features and confirmation of gene localisation to distal Xq28. Am J Med Genet 45(3):327–334. doi:10.1002/ajmg.1320450309

    Article  PubMed  CAS  Google Scholar 

  2. Adwani SS, Whitehead BF, Rees PG et al (1997) Heart transplantation for Barth syndrome. Pediatr Cardiol 18(2):143–145

    Article  PubMed  CAS  Google Scholar 

  3. Barth PG, Scholte HR, Berden JA et al (1983) An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. J Neurol Sci 62(1–3):327–355

    Article  PubMed  CAS  Google Scholar 

  4. Barth PG, Valianpour F, Bowen VM et al (2004) X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): an update. Am J Med Genet A 126A(4):349–354. doi:10.1002/ajmg.a.20660

    Article  PubMed  Google Scholar 

  5. Barth PG, Wanders RJ, Vreken P et al (1999) X-linked cardioskeletal myopathy and neutropenia (Barth syndrome) (MIM 302060). J Inherit Metab Dis 22(4):555–567

    Article  PubMed  CAS  Google Scholar 

  6. Bione S, D'Adamo P, Maestrini E et al (1996) A novel X-linked gene, G4.5. is responsible for Barth syndrome. Nat Genet 12(4):385–389. doi:10.1038/ng0496-385

    Article  PubMed  CAS  Google Scholar 

  7. Bleyl SB, Mumford BR, Thompson V et al (1997) Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome. Am J Hum Genet 61(4):868–872. doi:10.1086/514879

    Article  PubMed  CAS  Google Scholar 

  8. Cantlay AM, Shokrollahi K, Allen JT et al (1999) Genetic analysis of the G4.5 gene in families with suspected Barth syndrome. J Pediatr 135(3):311–315

    Article  PubMed  CAS  Google Scholar 

  9. D'Adamo P, Fassone L, Gedeon A et al (1997) The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies. Am J Hum Genet 61(4):862–867. doi:10.1086/514886

    Article  PubMed  Google Scholar 

  10. Gedeon AK, Wilson MJ, Colley AC, Sillence DO, Mulley JC (1995) X linked fatal infantile cardiomyopathy maps to Xq28 and is possibly allelic to Barth syndrome. J Med Genet 32(5):383–388

    Article  PubMed  CAS  Google Scholar 

  11. Hauff KD, Hatch GM (2006) Cardiolipin metabolism and Barth syndrome. Prog Lipid Res 45(2):91–101. doi:10.1016/j.plipres.2005.12.001

    Article  PubMed  CAS  Google Scholar 

  12. Houtkooper RH, Rodenburg RJ, Thiels C et al (2009) Cardiolipin and monolysocardiolipin analysis in fibroblasts, lymphocytes, and tissues using high-performance liquid chromatography–mass spectrometry as a diagnostic test for Barth syndrome. Anal Biochem 387(2):230–237. doi:10.1016/j.ab.2009.01.032

    Article  PubMed  CAS  Google Scholar 

  13. Ichida F, Tsubata S, Bowles KR et al (2001) Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation 103(9):1256–1263

    PubMed  CAS  Google Scholar 

  14. Johnston J, Kelley RI, Feigenbaum A et al (1997) Mutation characterization and genotype–phenotype correlation in Barth syndrome. Am J Hum Genet 61(5):1053–1058. doi:10.1086/301604

    Article  PubMed  CAS  Google Scholar 

  15. Kelley RI, Cheatham JP, Clark BJ et al (1991) X-linked dilated cardiomyopathy with neutropenia, growth retardation, and 3-methylglutaconic aciduria. J Pediatr 119(5):738–747

    Article  PubMed  CAS  Google Scholar 

  16. Kulik W, van Lenthe H, Stet FS et al (2008) Bloodspot assay using HPLC-tandem mass spectrometry for detection of Barth syndrome. Clin Chem 54(2):371–378. doi:10.1373/clinchem.2007.095711

    Article  PubMed  CAS  Google Scholar 

  17. Liang WC, Nishino I (2011) Lipid storage myopathy. Curr Neurol Neurosci Rep 11(1):97–103. doi:10.1007/s11910-010-0154-y

    Article  PubMed  CAS  Google Scholar 

  18. Neuwald AF (1997) Barth syndrome may be due to an acyltransferase deficiency. Curr Biol 7(8):R465–R466

    Article  PubMed  CAS  Google Scholar 

  19. Schlame M, Kelley RI, Feigenbaum A et al (2003) Phospholipid abnormalities in children with Barth syndrome. J Am Coll Cardiol 42(11):1994–1999

    Article  PubMed  CAS  Google Scholar 

  20. Schlame M, Towbin JA, Heerdt PM et al (2002) Deficiency of tetralinoleoyl-cardiolipin in Barth syndrome. Ann Neurol 51(5):634–637. doi:10.1002/ana.10176

    Article  PubMed  CAS  Google Scholar 

  21. Spencer CT, Bryant RM, Day J et al (2006) Cardiac and clinical phenotype in Barth syndrome. Pediatrics 118(2):e337–e346. doi:10.1542/peds.2005-2667

    Article  PubMed  Google Scholar 

  22. Spencer CT, Byrne BJ, Gewitz MH et al (2005) Ventricular arrhythmia in the X-linked cardiomyopathy Barth syndrome. Pediatr Cardiol 26(5):632–637. doi:10.1007/s00246-005-0873-z

    Article  PubMed  CAS  Google Scholar 

  23. Stein SM, Dale DC (2003) Molecular basis and therapy of disorders associated with chronic neutropenia. Curr Allergy Asthma Rep 3(5):385–388

    Article  PubMed  Google Scholar 

  24. Steward CG, Newbury-Ecob RA, Hastings R et al (2010) Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth. Prenat Diagn 30(10):970–976. doi:10.1002/pd.2599

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest to report.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan

    Atsuhito Takeda, Masafumi Yamada, Hirokuni Yamazawa & Tadashi Ariga

  2. Department of Pediatrics, Sapporo City General Hospital, 1-1, North 11, West 13, Chuo-ku, Sapporo, 060-8604, Japan

    Akira Sudo

  3. Department of Pediatric Cardiology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjukuku, Tokyo, 162-8666, Japan

    Gaku Izumi

  4. National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan

    Ichizo Nishino

Authors
  1. Atsuhito Takeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akira Sudo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masafumi Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hirokuni Yamazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gaku Izumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ichizo Nishino
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tadashi Ariga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Atsuhito Takeda.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takeda, A., Sudo, A., Yamada, M. et al. Eponym. Eur J Pediatr 170, 1365–1367 (2011). https://doi.org/10.1007/s00431-011-1575-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-011-1575-6

Keywords

Search

Navigation