Volume 130, Number 6 American Heart Journal Letters 1317

2. Kishida H, Cole, JS, Surawicz B. Negative U wave: a highly specific but poorly understood sign of heart disease. Am J Cardiol 1981;49:2030-6.

3. Scholl JM, Wagniart P, Morice MC, Charlier P, Morin B, Daffos C. Elimination of isolated exercise-induced U wave inversion after suc- cessful percutaneous transluminal coronary angioplasty oflei~ anterior descending artery. AM HEART J 1987;114:166-9.

4. Parodi O, Uthurralt N, Severi S, Bencivelli W, Michelassi C. L'Abbate M, Maseri A. Transient reduction of regional myocardial perfusion during angina at rest with ST-segment deparession or normalization of negative T waves. Circulation 1981;63:1238-47.

5. Dunn RF, Bailey IK, Uren R, Kelly DT. Exercise-induced ST segment elevation: correlation of thallium-201 myocardial perfusion scanning and coronary arteriography. Circulation 1980;61:989-95.

6. Yamakado T, Nakamo T, Masuola T, Takezawa HD. Coronary angio- graphic findings associated with U-wave inversion during coronary ar- tery spasm. Am J Cardiol 1987;60:188-90.

4 ] 8 ] 6 7 1 6 7

ALAGILLE SYNDROME (ARTERIOHEPATIC DYSPLASIA)

To the Editor: We read with interest the report of Silberbach et al. 1 about ar-

teriohepatic dysplasia and cardiovascular malformations. Syn- dromic paucity of interlobular bile ducts, also termed Alagille syndrome, is an uncommon cause of chronic intrahepatic cholesta- sis in pediatric age characterized by peculiar facies, intrahepatic biliary hypoplasia, heart diseases, vertebral arche defects, ocular abnormalities, growth retardation, mental deficiencies, and hy- pogonadism. 2 Since Alagille's first description of this syndrome, many reports pointed out its association with cardiac anoma- lies, 1-3 Peripheral pulmonary branch stenoses and/or hypoplasia account for the vast majority of the congenital heart defects, 4 al- though other simple congenital heart defects (tetralogy of Fallot, pulmonary valve stenosis, pulmonary valve atresia with ventric- ular septal defect, pulmonary valve atresia with intact ventricu- lar septum, aortic stenosis, anomalous pulmonary venous drain- age, ventricular septal defect, and atrial septal defect) have seldom been described. 1, 3 Among the 123 cases of Alagille syn- drome with cardiac malformations so far described, complex con- genital heart diseases have never been previously reported 1 un- like the well-known association between nonsyndromic extrahe- patic bile duct hypoplasia and complex congenital heart malformations. We report a never described case of complex con- genital heart malformation in a patient with Alagille syndrome.

A 3-week-old baby was hospitalized because of mild-to-moder- ate cyanosis and increasing jaundice. High direct bilirubin levels and high levels of alkaline phosphatase and aspartate transam- inase suggested cholestasis. At pediatric examination, the pheno- typic features of Alagille syndrome were found, although the chromosomic pattern was not assessed. By echocardiography and cardiac catheterization, a univentricular heart of right ventricu- lar type served by a common atrioventricular valve was diagnosed. The aorta originated from the right ventricle, but the pulmonary circulation depended on a closing ductus arteriosus because of pulmonary valve atresia. An aberrant right subclavian artery from a left aortic arch was found. After a systemic-to-pulmonary artery shunt (modified left Blalock-Taussig shunt), the arterial oxygen saturation markedly increased, but 2 weeks later the baby died from hepatic failure. At autopsy, the intracardiac anatomy was confirmed. The systemic-to-pulmonary shunt was patent, and the atresia of the intrahepatic biliary ducts was confirmed. Although necropsy data about the size and position of the spleen are not available, we suspect that this cardiac anomaly could have been part of a heterotaxic syndrome.

Giuseppe Santoro, MD Roberto Formigari, MD

Luigi Ballerini, MD Department of Pediatric Cardiology

Duccio Di Carlo Department of Surgery

Ospedale "Bambino Gesit" Piazza S. Onofrio, 4

00165 Rome, Italy

REFERENCES

1. Silberbach M, Lashley BA, Reller MD, Kinn WF, Terry A, Sunderland CO. Arteriohepatic dysplasia and cardiovascular malformations. AM HEART J 1994;127:695-9.

2. Alagille D, Odievre M, Gautier M, Dommerguess JP. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malforma- tion, retarded physical, mental, and sexual development, and cardiac murmur . J Pediatr 1975;86:63-71.

3. Greenwood RD, Rosenthal A, Crocker AC, Nadas AS. Syndrome ofin- trahepatic biliary disgenesis and cardiovascular malformations. Pedi- atrics 1976;58:243-7.

4. Alagille D, Estrada A, Hadchouel M, Gautier M, Odievre M, Dommer- gues M. Syndromic paucity of interlobular bile ducts (Alagille syn- drome or arteriohepatic dysplasia): review of 80 cases. J Pediatr 1987; 110:195-200.

418]67152

REPLY

To the Editor: The letter by Santoro et al. describes a 3-week-old infant with

signs, symptoms, and autopsy evidence of intrahepatic biliary atresia who had heart disease consisting of a single ventricle (right ventricular type) pulmonary atresia, common atrioventricular valve, and an aberrant right subclavian artery. There is no com- ment regarding the pulmonary venous anatomy or the relative size of the branch pulmonary arteries.

This case extends the spectrum of congenital heart diseases that have been associated with Alagille syndrome. In our review of 122 cases with sufficiently documented cardiac anatomy and histo- logic evidence ofintrahepatic biliary atresia, there were no cases of single ventricle, nor were there any instances of endocardial cushion defects. Of the cases we reviewed, 107 (88%) of 122 had either isolated peripheral pulmonary stenosis (PPS) or PPS asso- ciated with other heart defects. Thus it would be unusual if PPS were absent in this infant. As the authors point out, there is an association between complex cyanotic heart disease and extrahe- patic bile duct hypoplasia. What was the status of the extrahepatic biliary system in this infant? Information regarding the spleen, visceral situs, and pulmonary vein connections might prove help- ful in this regard because endocardial cushion defects are associ- ated with heterotaxy syndromes, and polysplenia (or asplenia) may occur in up to 30% of cases ofextrahepatic biliary atresia but not in Alagille syndrome. This raises the question of whether the findings in the 3-week-old infant are more representative of a group with combined extrahepatic and intrahepatic biliary atre- sia.

Michael Silberbach, MD Annie Terry, MD

Department of Pediatrics Doernbecher Children's Hospital

Oregon Health Sciences University 3181 SW Sam Jackson Park Road, UHNGO

Portland, OR 97201