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.
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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 |
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