Pediatr Cardiol 12:161-163, 1991
Pediatric Cardiology 9 Springer-VerlagNew York Inc. 1991
C a r d i o m y o p a l h y in G l y c o g e n - S t o r a g e D i s e a s e T y p e III: Clinical and E c h o g r a p h i c Study o f 18 P a t i e n t s Ph. Labrune, P. Huguet, and M. Odievre Service de P~diatrie Generale. H6pital Antoine Beclbre, Clamart. France
SUMMARY. Cardiac examinations were performed on 18 patients with glycogen-storage disease (GSD) type III. Clinical examination was always normal and the electrocardiograms revealed nonspecific data. Similarly, serum muscular enzyme activities were not useful in indicating the presence of cardiomyopathy. Echocardiographic evidence of myocardiopathy was found in five of the 16 children studied (mean age, 9.5 years). Echocardiographic parameters remained stable during the follow-up period (at least 3 years). The other 11 children had no echocardiographic evidence of cardiomyopathy. No relationship was found between peripheral myopathy and cardiomyopathy. All patients with GSD type III should be regularly investigated by echocardiography in respect of their cardiac muscle status. KEY WORDS: Glycogen-storage disease--Amylo-l,6-glucosidase--Cardiomyopathy--Echocardiography
Glycogen-storage disease (GSD) type III is an autosomal recessive disease due to a deficiency of amylo-l,6-glucosidase activity (debrancher enzyme) [4, 12]. Clinical symptoms and biological disturbances are usually related to decreased hepatic glycogenolysis (hepatomegaly and failure to thrive, hypoglycemia, and hyperlipemia). Occasionally, symptoms of myopathy may occur, since the enzyme deficiency has also been demonstrated in muscle. In this respect, cardiomyopathy is considered as potentially dangerous [7, 8], although its frequency and severity have not been evaluated in large series. Furthermore, no relationship has ever been found between skeletal myopathy and cardiomyopathy. The aim of this study is to report our findings in 18 patients with GSD type III, regularly followed in our clinic.
Patients and Methods Eighteen patients with GSD type Ill (10 boys and 8 girls) whose ages ranged from 8 months to 18 years were included in the study
Address ~ p r i n t s requests to: Dr. Ph. Labrune, Service de Pediatrie G6n6rale, H6pital Antoine B6clere, 157 rue de la Porte de Trivaux, 92141 Clamart Cedex, France.
(Table 1). Amylo-l,6-glucosidase activity was assayed in liver tissue and/or erythrocytes according to a previously described method, determining the incorporation of 14C-glucose in glycogen [3]. In the liver, control values ranged from 150-350 U/g liver; in erythrocytes, control values were 3.83 -+ 2.18 U/g hemoglobin. All children had reduced activity of amylo-l,6-glucosidase (< 10% of controls in liver and/or erythrocytes). Patients' muscle strength was graded, according to testing scores, as severe (daily handicap in routine life), moderate (difficulty in sporting activities at school), and absent. Serum muscular enzyme activities were regularly assayed (creatine kinase, aldolase, and lactate dehydrogenase). Cardiac evaluation included physical examination, electrocardiography (ECG), chest x-ray, and echocardiography (uniand bidimensional).
Results In three patients, there was evidence of severe skeletal myopathy; in six, myopathic symptoms were considered to be moderate; and nine patients had no symptoms (Table 1). A mild systolic murmur was heard in three patients; none ever had symptoms of heart failure. Creatine kinase serum activity was increased in 13 patients, irrespective of the evidence of echocardiographic signs of cardiomyopathy (Table 1). A1dolase and lactate dehydrogenase serum activities
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Pediatric Cardiology Vol. 12, No. 3, 1991
Table 1. Patient data Patients (sex)
Age (years)
I(M)" 2(M) 3(F)" 4(M)" 5(F) 6(F) 7(M) 8(M) 9(F) 10(F)" 11(M)" 12(F)" 13(F) 14(M)" 15(M)" 16(F)" 17(M)" 18(M)"
16 16 15 19 2 4 2 6 12 13 19 13 19 16 16 30 10 20
Peripheral myopathy
Echocardiographic data (age at diagnosis)
Moderate Severe Moderate Mode rate Moderate Absent Absent Absent Moderate Absent Absent Severe Absent Absent Absent Moderate Severe Absent
Normal Normal Normal Normal Normal ND ND Normal Cardiomyopathy Normal Normal Cardiomyopathy Normal Cardiomyopathy Normal Normal Cardiomyopathy Cardiomyopathy
(III
(10) (9)
(3) (15)
CPK (IU/L) (n < 80) 1745 1200 750 46 150 28 160 120 65 197 52 703 1270 75 2675 ND 652 806
ND, not done. " Echocardiographic follow-up, >3 years.
were irregularly increased (data not shown). Chest x-ray was always normal (in particular, no evidence of cardiomegaly was ever found). In four children, the ECG indicated left ventricular hypertrophy with normal sinus rhythm and high R wave voltages over the left precordium and left axis deviation. In three children, biventricular hypertrophy was suspected with normal sinus rhythm, left axis deviation, and right bundle branch block. In three children, the ECG was normal.
obstruction was detected. Four of these five children had abnormal ECGs with left ventricular hypertrophy. In the other 11 patients, echocardiography was considered to be normal. Echocardiographic follow-up was obtained in l 1 patients for a period of 3 years or more (Table 1). No significant changes were noted, either in children with evidence of cardiomyopathy or in those with normal echocardiography.
Discussion
Echographical Studies Echocardiography was not performed in two patients. The thickness of the septum and posterior wall of the left ventricle was compared with normal values: 6 mm (range, 5-7 ram) under 5 years of age (body surface, 0.6-1 m2); 7 mm (range, 6-8 ram) between 5 and 10 years (body surface, 1.I-1.5 m2); 8 mm (range, 7-8 mm) after 10 years (body surface, >1.5 m2). The control value for the septum/posterior wall ratio was
Pediatric Cardiology 9 Springer-VerlagNew York Inc. 1991
C a r d i o m y o p a l h y in G l y c o g e n - S t o r a g e D i s e a s e T y p e III: Clinical and E c h o g r a p h i c Study o f 18 P a t i e n t s Ph. Labrune, P. Huguet, and M. Odievre Service de P~diatrie Generale. H6pital Antoine Beclbre, Clamart. France
SUMMARY. Cardiac examinations were performed on 18 patients with glycogen-storage disease (GSD) type III. Clinical examination was always normal and the electrocardiograms revealed nonspecific data. Similarly, serum muscular enzyme activities were not useful in indicating the presence of cardiomyopathy. Echocardiographic evidence of myocardiopathy was found in five of the 16 children studied (mean age, 9.5 years). Echocardiographic parameters remained stable during the follow-up period (at least 3 years). The other 11 children had no echocardiographic evidence of cardiomyopathy. No relationship was found between peripheral myopathy and cardiomyopathy. All patients with GSD type III should be regularly investigated by echocardiography in respect of their cardiac muscle status. KEY WORDS: Glycogen-storage disease--Amylo-l,6-glucosidase--Cardiomyopathy--Echocardiography
Glycogen-storage disease (GSD) type III is an autosomal recessive disease due to a deficiency of amylo-l,6-glucosidase activity (debrancher enzyme) [4, 12]. Clinical symptoms and biological disturbances are usually related to decreased hepatic glycogenolysis (hepatomegaly and failure to thrive, hypoglycemia, and hyperlipemia). Occasionally, symptoms of myopathy may occur, since the enzyme deficiency has also been demonstrated in muscle. In this respect, cardiomyopathy is considered as potentially dangerous [7, 8], although its frequency and severity have not been evaluated in large series. Furthermore, no relationship has ever been found between skeletal myopathy and cardiomyopathy. The aim of this study is to report our findings in 18 patients with GSD type III, regularly followed in our clinic.
Patients and Methods Eighteen patients with GSD type Ill (10 boys and 8 girls) whose ages ranged from 8 months to 18 years were included in the study
Address ~ p r i n t s requests to: Dr. Ph. Labrune, Service de Pediatrie G6n6rale, H6pital Antoine B6clere, 157 rue de la Porte de Trivaux, 92141 Clamart Cedex, France.
(Table 1). Amylo-l,6-glucosidase activity was assayed in liver tissue and/or erythrocytes according to a previously described method, determining the incorporation of 14C-glucose in glycogen [3]. In the liver, control values ranged from 150-350 U/g liver; in erythrocytes, control values were 3.83 -+ 2.18 U/g hemoglobin. All children had reduced activity of amylo-l,6-glucosidase (< 10% of controls in liver and/or erythrocytes). Patients' muscle strength was graded, according to testing scores, as severe (daily handicap in routine life), moderate (difficulty in sporting activities at school), and absent. Serum muscular enzyme activities were regularly assayed (creatine kinase, aldolase, and lactate dehydrogenase). Cardiac evaluation included physical examination, electrocardiography (ECG), chest x-ray, and echocardiography (uniand bidimensional).
Results In three patients, there was evidence of severe skeletal myopathy; in six, myopathic symptoms were considered to be moderate; and nine patients had no symptoms (Table 1). A mild systolic murmur was heard in three patients; none ever had symptoms of heart failure. Creatine kinase serum activity was increased in 13 patients, irrespective of the evidence of echocardiographic signs of cardiomyopathy (Table 1). A1dolase and lactate dehydrogenase serum activities
162
Pediatric Cardiology Vol. 12, No. 3, 1991
Table 1. Patient data Patients (sex)
Age (years)
I(M)" 2(M) 3(F)" 4(M)" 5(F) 6(F) 7(M) 8(M) 9(F) 10(F)" 11(M)" 12(F)" 13(F) 14(M)" 15(M)" 16(F)" 17(M)" 18(M)"
16 16 15 19 2 4 2 6 12 13 19 13 19 16 16 30 10 20
Peripheral myopathy
Echocardiographic data (age at diagnosis)
Moderate Severe Moderate Mode rate Moderate Absent Absent Absent Moderate Absent Absent Severe Absent Absent Absent Moderate Severe Absent
Normal Normal Normal Normal Normal ND ND Normal Cardiomyopathy Normal Normal Cardiomyopathy Normal Cardiomyopathy Normal Normal Cardiomyopathy Cardiomyopathy
(III
(10) (9)
(3) (15)
CPK (IU/L) (n < 80) 1745 1200 750 46 150 28 160 120 65 197 52 703 1270 75 2675 ND 652 806
ND, not done. " Echocardiographic follow-up, >3 years.
were irregularly increased (data not shown). Chest x-ray was always normal (in particular, no evidence of cardiomegaly was ever found). In four children, the ECG indicated left ventricular hypertrophy with normal sinus rhythm and high R wave voltages over the left precordium and left axis deviation. In three children, biventricular hypertrophy was suspected with normal sinus rhythm, left axis deviation, and right bundle branch block. In three children, the ECG was normal.
obstruction was detected. Four of these five children had abnormal ECGs with left ventricular hypertrophy. In the other 11 patients, echocardiography was considered to be normal. Echocardiographic follow-up was obtained in l 1 patients for a period of 3 years or more (Table 1). No significant changes were noted, either in children with evidence of cardiomyopathy or in those with normal echocardiography.
Discussion
Echographical Studies Echocardiography was not performed in two patients. The thickness of the septum and posterior wall of the left ventricle was compared with normal values: 6 mm (range, 5-7 ram) under 5 years of age (body surface, 0.6-1 m2); 7 mm (range, 6-8 ram) between 5 and 10 years (body surface, 1.I-1.5 m2); 8 mm (range, 7-8 mm) after 10 years (body surface, >1.5 m2). The control value for the septum/posterior wall ratio was
