Echocardiographic Findings in Pompe s Disease with Left Ventricular Obstruction

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1 Clin. Cardiol. 8, (1985) 0 Clinical Cardiology Publishing Co., Inc. Echocardiographic Findings in Pompe s Disease with Left Ventricular Obstruction Y. SHAPIR, M.D., N. ROGUIN, M.D Department of Cardiology, Rambam Medical Center, and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel Summary: Two infants with Pompe s disease (type I1 glycogenosis) showing echocardiographic evidence of obstructive cardiomyopathy are described. On M-mode and two-dimensional (2-D) echocardiography there was a severe hypertrophy of the interventricular septum, free, and posterior left ventricular wall with midsystolic closure of the aortic valve. The combined echocardiographic and electrocardiographic findings are helpful in the clinical diagnosis of this severe disease. Key words: echocardiography, Pompe s disease, left ventricular outflow obstruction Introduction Type I1 glycogenosis (Pompe s disease) is characterized by muscular weakness, hypotonia, and enlargement of the heart and liver, followed by progressive cardiorespiratory failure. Most patients die by the age of one *Present affiliation: Dept. of Pediatric Cardiology, U.C.L.A. School Medicine, Los Angeles, California Address for reprints: N. Roguin, M.D. Dept. of Cardiology Rambain Medical Center Haifa 35254, Israel Received: July 6, 1984 Accepted: September 4, 1984 year and almost all by the age of two years (Pompe, 1932, 1933; Rudolph, 1977). In Pompe s disease there is a massive thickening of the myocardium. An anatomic ventricular outflow tract obstruction, secondary to the myocardial hypertrophy, is also occasionally present (Ehlers er al., 1962; Hohn et a(., 1965; Rees er al., 1976). The purpose of our report is to describe the echocardiographic (Mmode and two-dimensional echocardiography) findings in two patients with Pompe s disease with signs of obstructive cardiomyopathy. Case No. 1 A six-month-old male infant, born to parents who were first-degree cousins. Pregnancy and delivery were normal. Four other children of this couple died within a few months after delivery. At the age of three months, the infant suffered from an upper respiratory infection with normal chest x-ray. After this episode, the child suffered from progressive weakness and prolonged cough. Two days before admission he became apathetic and dyspneic. On admission, a weak and underweight infant, who was dyspneic and mildly cyanotic with marked hyptonia and in froglike position was noticed. No deep tendon reflexes were found, a grade IIWI systolic ejection murmur was heard at the left sternal border, and normal peripheral pulses were felt. The liver edge was palpated 4 cm below the right costal margin. Workup Sepsis workup was negative and so was the sequential serologic workup. Muscle biopsy showed glycogen storage disease, and tk liver needle biopsy revealed

2 I82 Clin. Cardiol. Vol. 8, March 1985 hepatocytes full of glycogen with a conserved basic structure. An enzymatic study confirmed the diagnosis by finding 15 % more than normal control acid maltase in the muscle. The sample was rich with glycogen. Cardiac Findings Electrocardiogram examination showed short P-R interval, peaked P waves with right ventricular hypertrophy, and severe left ventricular hypertrophy with ST-T changes. Echocardiogram (M-mode) showed severe hypertrophy of the septum and posterior left ventricular wall and midsystolic closure of the aortic valve (Fig. 1, Table I). Twodimensional echocardiography (2D) revealed hypertrophy of the papillary muscles. There was a complete obstruction of the left ventricular cavity at end-systole (Fig. 2). The chest x-ray revealed a boot-shaped heart with signs of venocapillary hypertension. The child was treated with oxygen, diuretics, and beta blockers, but despite intensive therapy he died 25 days after admission. The parents refused postmortem examination. Case No. 2 A 5-month-old female infant, product of a normal pregnancy and delivery. From the family history it is important to note that four uncles of the patient had died before the age of one year due to cardiac reasons (no postmortem examination was done due to their religious belief). At the age of two months, hypotonia and hepatomegaly were noted. At the age of four months the baby suffered from a left lung pneumonia. After this episode the patient developed progressive weakness, dyspnea, and cough. On admission we noted she was in poor general condition, underweight, hypotonic, and dyspneic. A grade III/VI systolic ejection murmur was heard at the left sternal border, there were normal peripheral pulses. The liver edge was palpated 3.5 cm below the right costal margin. No deep tendon reflexes were found. Workup Positive findings were: muscle biopsy showed glycogen storage disease and the liver needle biopsy revealed hepatocytes full of glycogen. An enzymatic study confirmed the diagnosis by finding 15% more than normal control acid maltase in the muscle. Cardiac Findings Chest x-ray examination showed a large heart with signs of venocapillary hypertension. The electrocardiogram showed short P-R interval, peaked P waves, severe right and left ventricular hypertrophy with ST-T changes (Fig. 3), M-mode echocardiogram (Table I) showed severe hypertrophy of the septum and left ventricular posterior wall (Figs. 4, 6) with midsystolic closure of the aortic valve (Fig. 5). There was aortic mitral continuity and aortic septal continuity (Fig. 6). Two-dimensional echocardiography revealed severe hypertrophy of the septum, free, and posterior left ventricular wall. The child was treated with diuretics, oxygen, and beta blockers without showing any clinical improvement. At the age of six months the patient is alive but in very poor general condition. Discussion FIG I M-mode echocardiography showing midsystolic closure of the aortic valve. (Patient No. 1.) Glycogen storage disease of the heart (glycogen storage disease type I1 or Pompe s disease) is a rare hereditary error of carbohydrate metabolism in which excessive quantities of the glycogen accumulate in the heart, muscle and other tissues (Ehlers et al., 1962; Pompe, 1932, 1933). The condition appears to be transmitted as an autosomal recessive disorder. There is a disproportionate number of affected males. An absence of lysosonial alpha-glucosidase has bccn demonstrated in the tissues of these patients. With elec-

3 ~ ~ ~~~ Y. Shapir and N. Roguin: Echocardiography in Pompe s disease I83 TABLE I M-mode echocardiographic quantitative measurements and calculations Patient (cm) No. 1 No. 2 Normal range for weight (cm) Aortic Root LA (ESD) LV (ESD) LV (EDD) RV Septum (EDD) LVPW thickness (EDD) Shortening fraction Ejection fraction o % 95 % o 37% 75 % oo % % Abbreviations: LA =left atrium, ESD =end-systolic dimension, EDD =end-diastolic dimension, RV = right ventricle, LV = left ventricle, LVPW =left ventricular posterior wall. FIG 2 Two-dimensional echocardiography. Short-axis view showing hypertrophy of the left ventricular wall with almost complete obliteration of the left ventricular cavity during systole. (Patient No. 1.) Vl(%?) vp(%) V3(l/2) Vq( /Z) v5( /2) vs( /2) ST FIG. 3 ECG tracing showing short P-R interval, right and left ventricular hypertrophy, and ST-T changes. (Patient No. 2.)

4 184 Clin. Cardiol. Vol. 8, March 1985 FIG. 4 M-mode echocardiography showing midsystolic closure of the aortic valve. (Patient No. 2.) Ao: aorta, LA: left atrium. Fa. 5 M-mode echocardiography showing severe hypertrophy of the interventricular septum. (Patient No. 2.). RV: right ventricle; S: septum; LV: left ventricle FIG 6 M-mode echocardiography: Sweep aorta to left ventricle. (Patient No. 2.)

5 Y. Shapir and N. Roguin: Echocardiography in Pompe s disease I85 tron microscopy, engorgement of the lysosomes with glycogen can be demonstrated, whereas, the amount of cytoplasmatic glycogen appears normal. No effective treatment is known (Rudolph, 1977). An anatomic ventricular outflow obstruction secondary to the myocardial hypertrophy is occasionally present in Pompe s disease (Ehlers et al., 1962; Hohn et ul., 1965; Rees et al., 1976) and has been documented by echocardiography (Rees et al., 1976) and hemodynamic studies (Hohn et al., 1965; Rees ez al., 1976). Riggs et al. (1980), described the clinical presentation, echocardiographic, and hemodynamic data in 2 1 pediatric patients with dynamic left ventricular obstruction. They concluded that the spectrum of hypertrophic cardiomyopathy appears to be broader in the pediatric patients than in adults. None of the patients described suffered from Pompe s disease. Several forms of uncommon subaonic obstruction are known (Moss, 1977) and include: (1) valvar and subvalvular aortic stenosis in a tunnel-like narrowing of the left ventricular outflow tract, (2) anomalous basal attachment of the anterior leaflet of the mitral valve with accessory tissue of the valve and fusion with the interventricular septum, (3) a parachute deformity of the mitral valve in association with supravalvular stenosis of the left atrium, (4) some atrioventricular canal malformations, and (5) complications from postoperative pulmonary artery banding for ventricular septa1 defect and in Pompe s disease. This report describes two patients with clinical findings suggestive of Pompe s disease confirmed by pathological and metabolic studies. The cardiac status of obstructive cardiomyopathy in our patients is demonstrated by the M-mode echocardiogram showing severe hypertrophy of the septum and posterior wall and midclosure of the aonic valve (Figs. 1, 3, 4-6 and Table I). The twodimensional echocardiogram showed marked hypertrophy of the left ventricular wall and papillary muscle with complete obliteration of the cavity at end-systole (Fig. 2). Both patients presented the well-described findings of the electrocardiogram in Pompe s disease (Ehlers et ul., 1962; Hohn et ul., 1965; Moss el al., 1974; Rudolph, 1977); short PR interval, large QRS complexes, and ST-T changes. We feel that the electrocardiographic (Fig. 3) together with the echocardiographic findings (M-mode and 2-D) are very helpful in the noninvasive diagnosis of Pompe s disease. References Ehlers KH, Hagstrom JWC, Lucas DS, Redo SF, Engle MA: Glycogen storage disease of the mocadium with obstruction of the left ventricular outflow. Circulation 25, 96 ( 1962) Hohn AR, Lowe CU, Sokal JE and Lamben EC: Cardiac problems in the glycogenoses with specific reference to Pompe s disease. Pediatrics 35, 313 (1965) Moss AJ: Heart Disease in Infants, Children and Adolescents. Second Edition. Williams & Wilkins, Baltimore- London (1977) 185, 186 Moss A, Adams FW, Emmanoulides GL: Heart Disease in Znfanrs. ChiMren and Adolescents. William & Wilkins, Baltimore (1974) Pompe JC: Over Idiopatische hypertrophie van het heart. Nederl Tijdschr Geneesk 76, 304 (1932) Pompe JC: Hypertrophic d idiopathique du coeur. Ann Path Anat 10, 1 (1933) Rees A, Elbl F, Minhas K, Solinger R: Echocardiographic evidence of outflow obstruction in Pompe s disease (Glycogen storage disease of the heart ) Am J Cardio/ 37, 1103 (1976) Riggs T, Hirschfeld S, Rajai H: The pediatric spectrum of dynamic left ventricular obstruction. Am HeartJ 99,301 ( 1980) Rudolph AM: Pediatrics, 16th Edition. Appleton-Century- Crofts, New York (1977) 731