What are the clinical symptoms in layman's terms?
The classic symptoms in patients with Barth Syndrome are endocardial fibroelastosis, abnormally shaped mitochondria, neutropenia, and transitory lactic acidosis (see the definitions below). However, the variety, severity, and number of symptoms varies from patient to patient. It is thought that the abnormalities in heart function are secondary to problems with mitochondrial function, and that these are produced by a primary metabolic abnormality such as a missing enzyme function (perhaps an acyltransferase enzyme in the mitochondrion).
dilated cardiomyopathy: A disease of the myocardium (middle layer of the heart, consisting of cardiac muscle). There is a decreased function of the left ventricle associated with its dilation.
endocardial fibroelastosis (E.F.): The left ventricle of the heart shows an increased thickness, with (abnormally abundant) elastic and collagenous fibers. This may cause the left ventricle to not push blood as well. Severely affected Barth Syndrome patients can die of E.F. See the below diagram. The drawing on the left shows a normal heart including the left ventricle and wall. The picture on the right shows E.F. of the left ventricle. Notice the fibrous thickening.
cardiac and skeletal myopathy: Myopathy is any abnormal condition or disease of muscle tissue. Poor muscle tone is also observed in these patients.
short stature: Barth Syndrome patients are usually smaller and lighter than other newborns. They usually rank in the lower percentile for birth length and weight.
neutropenia: Reduced numbers of mature certain white blood cells (neutrophils), which are produced by the bone marrow. This may lead to an increased susceptibility to infection, particulary mouth sores. Neutropenia may be chronic or cyclic.
elevated urinary organic acids: Many patients have shown a rise in certain excreted organic acids in their urine and blood. This clinical finding is usually sporadic and transitory. Barth syndrome patients often show signs of 3-methylglutaconic aciduria, and 2-ethylhydracrylic aciduria. These may include a rise in lactic acid, 2-ketoglutaric acid, fumaric acid, hydroxybutyric acid, methyl glutaconic acid, methyl glutaric acid, and methyl hydracrylic acid.
abnormal mitochondria: The mitochondria are organelles that are found in the cytoplasm of most human cells and produce most of the cellular energy. In Barth Syndrome, patients may have some mitochondria that are abnormally shaped and/or that have unusual "inclusion bodies" containing abnormally stored material (such as glycogen). Diagram 3 is an illustration of a normal mitochondrion. The drawing on the left shows a cross-sectional view, and the photograph on the right shows a normal cardiac muscle mitochondrion. Diagram 4, shows abnormal mitochondria from a patient with Barth Syndrome. Notice that the mitochondria shown have abnormally shaped inner membranes and contain large, inclusion bodies. It should be noted that the abnormal mitochondria are very large and swollen.
The bottom two photos are from Neustein, H.B. et al. "An X-Linked Recessive Cardiomyopathy with Abnormal Mitochondria." Pediatrics, Vol. 64. No. 1. July 1979.
impaired oxidative phosphorylation machinery: There is evidence that some Barth Syndrome patients may have reduced activity of oxidative phosphorylation enzymes in their inner mitochondrial membranes. Oxidative phosphorylation is a biochemical pathway that is coupled to ATP synthesis. ATP is the main source of cellular energy. Some scientists hypothesize that a reduction in a cell's ability to produce enough cellular energy may help explain some Barth Syndrome symptoms.
Last Updated 06/20/00 by the Metz Lab.