Barth syndrome is an X-linked recessive disorder affecting only males. The clinical features of Barth syndrome include cardiomyopathy, endocardial fibroelastosis, neutropenia, hypocholesterolemia, growth retardation, short stature and cyclic acidurias which include increased levels of 3- methylglutaconic, 3-methylglutaric and 2-ethylhydracrylic acids. Abnormal mitochondria structure including dense granular inclusions are also present in Barth patients. This disorder is most often fatal due to cardiomyopathy and/ or sepsis. Almost half the patients that die of Barth syndrome do so because of neutropenia-related infection. If male infants can survive the initial aciduria cycle, they may begin to thrive despite continued intermittent cyclic bouts of aciduria. Mitochondrial dysfunction may contribute to the myopathy and cardiomyopathy of some patients with Barth syndrome. The incidence of Barth syndrome appears to occur at a rate similar to that of other rare recessive metabolic diseases, somewhere between 1 in 50,000 to 1 in 1 50,000 births. The function of the Barth (BTHS) gene is currently unknown, although several hypotheses have been formed and tested. The current reasoning describes the BTHS gene encoding a protein that belongs to a specific class of acyltransferases. This acyltransferase transfers acyl groups from Coenzyme A to glycerol phosphate in the formation of phospholipids integral to cell membranes. The purpose of this research was to expand our understanding of the molecular pathophysiology of Barth syndrome by performing mutation analysis of the BTHS gene in three unrelated males affected with Barth syndrome and four possible heterozygous female carriers. By use of polymerase chain reaction and automated DNA sequencing, analysis of genomic DNA identified a point mutation within the BTHS region of each affected male.Includes bibliographical references (leaves 60-64)California State University, Northridge. Department of Biology
