First-degree atrioventricular block and restrictive physiology as cardiac manifestations of Fabry's disease. (Case Report).

Abstract

Fabry's disease is an X-linked disorder of glycosphingolipid catabolism related to the defective activity of glycosphingolipid, mainly ceramide trihexoside, in the vascular smooth muscle, myocardium, cells of the sympathetic central nervous system, and epithelial cells of renal glomeruli. We describe a young man who had Fabry's disease arid unusual electrocardiographic and echocardiographic patterns at admission for treatment of left leg cellulitis. Findings included a prolonged PR interval and a right bundle branch block pattern, no echocardiographic signs of septal or hypertrophic cardiomyopathy, and a restrictive physiologic pattern. This pattern of electrocardiographic and echocardiographic characteristics of Fabry's disease has not been reported previously and should be added to the other cardiac manifestations of Fabry's disease.

Key Words: conduction defects, Fabry's disease, first-degree atrio-ventricular block, restrictive physiology, right bundle branch block

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Fabry's disease is an X-linked disorder of glycosphingolipid catabolism that results from the defective activity of glycosphingolipid, mainly ceramide trihexoside, in the vascular smooth muscle, myocardium, cells of sympathetic central nervous system, and epithelial cells of renal glomeruli. We present a case of Fabry's disease in which the patient was admitted because of left leg cellulitis and was found to have an unusual electrocardiographic and echocardiographic pattern.

Discussion

Fabry's disease is an X-linked recessive disorder of glycosphingolipid catabolism caused by a deficiency of the lysosomal enzyme [alpha]-galactosidase A as a consequence of one or more than four dozen mutations. (1,2) The disease is characterized by an intracellular accumulation of a neutral glycolipid with prominent involvement of the skin and kidneys as well as the myocardium in the classic form. The histologic examination often reveals widespread involvement of the myocardium, vascular endothelium, conducting tissues, and valves, particularly the mitral valve. (3) The major clinical manifestations of the disease result from the accumulation of the glycolipid substrate in endothelial cells, with eventual occlusion of small arterioles. The accumulation of the glycolipid occurs in the lysosomes of the cardiac tissues and is responsible for the multiple cardiovascular manifestations of Fabry's disease. The cardiac manifestations typically include angina pectoris and myocardial infarction despite angiographical ly normal coronary arteries (because of the accumulation of lipid moieties in coronary endothelial cells), increased left ventricular wall thickness simulating hypertrophic cardiomyopathy (because of accumulation in myocytes), left ventricular dysfunction and failure, and mitral regurgitation (because of deposition in valvular fibroblasts). (3) Symptomatic cardiovascular involvement occurs eventually in most affected males, whereas female carriers usually are asymptomatic or only minimally symptomatic. Systemic hypertension, mitral valve prolapse, and congestive heart failure are common clinical manifestations. The echocardiographic manifestations include atrioventricular block or a short PR interval, as well as ST segment and T wave abnormalities. (4) The echocardiogram usually reveals increased left ventricular wall thickness as a result of glycolipid deposition, which may simulate hypertrophic cardiomyopathy. (3)

Our patient was a 26-year-old man who had no symptoms of heart failure or angina pectoris. Unlike previously described patients, he had a prolonged PR interval and not a short one (ie, first-degree atrioventricular block by definition) with a right bundle branch block pattern as reported previously. The echocardiographic data are interesting and unique, because this report describes the first published case of Fabry's disease and restrictive physiology without any signs of hypertrophic cardiomyopathy (concentric, septal, or any other left ventricular enlargement). This previously unreported pattern of echocardiographic and echocardiographic characteristics of Fabry's disease should be added to the other cardiac manifestations of Fabry's s disease.

Accepted April 26, 2002.

References

(1.) Eng CM, Desnick RI. Molecular basis of Fabry disease: Mutations and polymorphisms in the human [alpha]-galactosidase A gene. Hum Mutat. 1994;3:103-111.

(2.) Ishii S, Kase R, Sakuraba H, Suzuki Y. Characterization of a mutant [alpha]galactosidase gene product for the late-onset cardiac form of Fabry disease. Biochem Biophys Res Commun 1993;197:1585-1589.

(3.) Eng CM, Resnick-Silverman LA, Niehaus DJ, Astrin KH, Desnick RJ. Nature and frequency of mutations in the [alpha]-galactosidase A gene that cause Fabry disease. Am J Hum Genet 1993;53:1186-1197.

(4.) Pochis WT, Litzow JT, King BG, Kenny D. Electrophysiologic findings in Fabry's disease with a short PR interval. Am J Cardiol 1994;74:203-204.

RELATED ARTICLE: Key Points

* A case of Fabry's disease with cardiac manifestations is described.

* Fabry's disease is characterized by PR interval prolongation and a right bundle branch block pattern seen on the electrocardiogram.

* Our patient demonstrated a restrictive physiologic pattern on the echocardiogram.

Case Report

A 26-year-old man was admitted with left leg cellulitis and high fever. Fabry's disease had been diagnosed years earlier on the basis of skin lesions and a biopsy performed elsewhere. His physical examination was unremarkable, except for his swollen, red left leg. The heart sounds were clear, and no pathologic sounds or murmurs were heard. The results of the cardiovascular and neurologic examinations were within normal limits. Chest x-ray films showed a normal cardiac shadow with no abnormalities in the peripheral lung fields or in the mediastinum. The electrocardiogram showed normal sinus rhythm (94 beats/mm), QRS axis of 60 degrees, and PR interval of 0.2 seconds. The QRS complex showed a right bundle branch block pattern with left ventricular enlargement. The electrocardiogram showed cardiac chambers of normal size and normal left ventricular systolic function without left ventricular hypertrophy. The valves were normal without stenosis or insufficiency, except for minimal mitral regurgitation. There was a restrictive physiology pattern of the left ventricle, however, with isovolumic relaxation time of 50 milliseconds, deceleration time of 160 milliseconds, and early to late diastolic filling ratio of 2.

From the Department of Internal Medicine A, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, and the Department of Internal Medicine A, Poria Hospital, Lower Galilee, Israel.

Reprint requests to Arnon Blum, MD, Department of Internal Medicine A, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel. Email: [e-mail]

Copyright [c] 2003 by The Southern Medical Association 0038-4348/03/9602-0212