HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schlame, M. Articles by Blanck, T. J. J. Search for Related Content PubMed PubMed Citation Articles by Schlame, M. Articles by Blanck, T. J. J.

CLINICAL RESEARCH: CONGENITAL HEART DISEASE/DOCHEAD>

Phospholipid abnormalities in children with Barth syndrome

Michael Schlame, MD^*,*, Richard I. Kelley, MD, PhD, Annette Feigenbaum, MB, ChB, Jeffrey A. Towbin, MD, Paul M. Heerdt, MD, PhD^||, Thomas Schieble, MD^*, Ronald J. A. Wanders, PhD^¶, Salvatore DiMauro, MD^# and Thomas J. J. Blanck, MD, PhD^*

^* Department of Anesthesiology, New York University School of Medicine, New York, New York, USA
Division of Metabolism, Kennedy Krieger Institute, Baltimore, Maryland, USA
Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada
Department of Pediatrics (Cardiology), Baylor College of Medicine, Houston, Texas, USA
^|| Department of Anesthesiology, Weill Medical College of Cornell University, New York, New York, USA
^¶ Laboratory of Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands
^# Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA

Manuscript received February 26, 2003; revised manuscript received June 9, 2003, accepted June 30, 2003.

^* Reprint requests and correspondence: Dr. Michael Schlame, Department of Anesthesiology, New York University School of Medicine, 550 First Avenue, New York, New York, USA 10016.
michael.schlame{at}med.nyu.edu

OBJECTIVES: We sought to identify characteristic lipid abnormalities in patients with Barth syndrome (BTHS) and to correlate the lipid profile to phenotype and genotype.

BACKGROUND: Barth syndrome typically includes cardiomyopathy, skeletal myopathy, neutropenia, growth retardation, and 3-methylglutaconic aciduria, and it is commonly associated with mutations in the tafazzin (TAZ) gene, whose products are homologous to phospholipid acyltransferases. However, clinical features of BTHS have also been found in patients with normal TAZ gene.

METHODS: We analyzed molecular species of phospholipids in left and right ventricle, skeletal muscle, platelets, lymphoblasts, and fibroblasts from 19 children with BTHS (positive TAZ mutation), 6 children with BTHS-like syndromes (wild-type TAZ), 4 children with isolated cardiomyopathy (wild-type TAZ), and various controls.

RESULTS: Cardiolipin, the specific lipid found only in mitochondria, was decreased in all tissues from BTHS patients, whereas concentrations of other phospholipids were normal. The molecular composition of cardiolipin was altered in all tissues from BTHS patients. The molecular compositions of phosphatidylcholine and phosphatidylethanolamine were altered in the heart. Cardiolipin abnormalities were only found in children with true BTHS, not in children with BTHS-like disease or with isolated cardiomyopathy. The degree of cardiolipin deficiency was tissue-specific but did not correlate with severity or specific phenotypic expression of BTHS.

CONCLUSIONS: Abnormal cardiolipin is a specific diagnostic marker of cardiomyopathies caused by TAZ mutations. These mutations lead to alterations in the fatty acid composition of several phospholipids, supporting the idea that TAZ encodes a human acyltransferase.

Abbreviations and Acronyms   BTHS = Barth syndrome   DCM = dilated cardiomyopathy   HPLC = high-performance liquid chromatography   ICM = ischemic cardiomyopathy   LV = left ventricle   RV = right ventricle   TAZ = tafazzin

This article has been cited by other articles:

				M. Schlame Thematic Review Series: Glycerolipids. Cardiolipin synthesis for the assembly of bacterial and mitochondrial membranes J. Lipid Res., August 1, 2008; 49(8): 1607 - 1620. [Abstract] [Full Text] [PDF]

				W. Kulik, H. van Lenthe, F. S. Stet, R. H. Houtkooper, H. Kemp, J. E. Stone, C. G. Steward, R. J. Wanders, and F. M. Vaz Bloodspot Assay Using HPLC-Tandem Mass Spectrometry for Detection of Barth Syndrome Clin. Chem., February 1, 2008; 54(2): 371 - 378. [Abstract] [Full Text] [PDF]

				F. Hullin-Matsuda, K. Kawasaki, I. Delton-Vandenbroucke, Y. Xu, M. Nishijima, M. Lagarde, M. Schlame, and T. Kobayashi De novo biosynthesis of the late endosome lipid, bis(monoacylglycero)phosphate J. Lipid Res., September 1, 2007; 48(9): 1997 - 2008. [Abstract] [Full Text] [PDF]

				G. C. Sparagna, A. J. Chicco, R. C. Murphy, M. R. Bristow, C. A. Johnson, M. L. Rees, M. L. Maxey, S. A. McCune, and R. L. Moore Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure J. Lipid Res., July 1, 2007; 48(7): 1559 - 1570. [Abstract] [Full Text] [PDF]

				A. J. Chicco and G. C. Sparagna Role of cardiolipin alterations in mitochondrial dysfunction and disease Am J Physiol Cell Physiol, January 1, 2007; 292(1): C33 - C44. [Abstract] [Full Text] [PDF]

				Y. Xu, A. Malhotra, M. Ren, and M. Schlame The Enzymatic Function of Tafazzin J. Biol. Chem., December 22, 2006; 281(51): 39217 - 39224. [Abstract] [Full Text] [PDF]

				M. A. van Werkhoven, D. R. Thorburn, A. K. Gedeon, and J. J. Pitt Monolysocardiolipin in cultured fibroblasts is a sensitive and specific marker for Barth Syndrome J. Lipid Res., October 1, 2006; 47(10): 2346 - 2351. [Abstract] [Full Text] [PDF]

				Y. Xu, M. Condell, H. Plesken, I. Edelman-Novemsky, J. Ma, M. Ren, and M. Schlame A Drosophila model of Barth syndrome PNAS, August 1, 2006; 103(31): 11584 - 11588. [Abstract] [Full Text] [PDF]

				S. M. Claypool, J. M. McCaffery, and C. M. Koehler Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins J. Cell Biol., July 31, 2006; 174(3): 379 - 390. [Abstract] [Full Text] [PDF]

				F. Valianpour, V. Mitsakos, D. Schlemmer, J. A. Towbin, J. M. Taylor, P. G. Ekert, D. R. Thorburn, A. Munnich, R. J. A. Wanders, P. G. Barth, et al. Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis J. Lipid Res., June 1, 2005; 46(6): 1182 - 1195. [Abstract] [Full Text] [PDF]

				Y. Yang, J. Cao, and Y. Shi Identification and Characterization of a Gene Encoding Human LPGAT1, an Endoplasmic Reticulum-associated Lysophosphatidylglycerol Acyltransferase J. Biol. Chem., December 31, 2004; 279(53): 55866 - 55874. [Abstract] [Full Text] [PDF]

				Y. Xu, R. I. Kelley, T. J. J. Blanck, and M. Schlame Remodeling of Cardiolipin by Phospholipid Transacylation J. Biol. Chem., December 19, 2003; 278(51): 51380 - 51385. [Abstract] [Full Text] [PDF]