Case Reports
Alagille Syndrome: A Case Report
中華放射醫誌　Chin J Radiol 1998；23(2)：61-63
Mo-Kiu Lau　Chin-Ming Jeng　Wen-Yu Lee　Ching-Tsuen Shen1
Yung-Cheng Wang　Chau-Ying Wu　Ching-Hwei Kung
Department of Radiology and Pediatrics1, Cathay General Hospital

ABSTRACT
　Arteriohepatic dysplasia (Alagille syndrome ) is a condition of chronic cholestasis in infancy associated with odd facies, pulmonic stenosis, butterfly vertebra and other abnormalities. The pathologic hallmark of arteriohepatic dysplasia is a paucity or absence of intrahepatic bile ducts. We present a 4-year-old boy with MRI study of heart showing peripheral stenosis of the left pulmonary artery and single butterfly vertebra. Ophthalmal examination discovered embryotoxon of both eyes. Scintigraphy revealed normal excretion of Tc-99m IDA into the intestine from the liver and liver biopsy exhibited paucity of intrahepatic bile ducts.

Key words: pulmonary arterial stenosis, cholestasis, MRI

INTRODUCTION
　Arteriohepatic dysplasia, also known as Alagille syndrome , is a syndrome complex of unknown etiology characterized by infantile cholestasis, pulmonic stenosis , eye abnormalities, vertebral defects and distinctive facies including small triangular face, broad forehead, pointed mandible, flattened cheeks, hypertelorism, deep-set eyes & prominent ears. Previous studies have defined the syndrome in older children and adults. However, when these patients present in infancy with cholestasis, the characteristic features may be incompletely developed and the diagnosis between syndromic and nonsyndromic types of paucity of interlobular bile ducts becomes difficult. Nonsyndromic paucity includes rubella or cytomegalovirus infections, alfa 1-antitrypsin deficiency and trisomy 21. Syndromic paucity has generally been thought to have a better long-term prognosis than nonsyndromic one.

CASE REPORT
　A 4 year-old boy had prolonged jaundice since the fifth day after birth and was admitted when he was 2 months old. Physical examination showed icteric sclera, yellow skin and hepatomegaly. Systolic murmur was heard at left upper sternal border radiating to left axillary region. Echocardiogram showed mild peripheral left pulmonic arterial stenosis and interatrial left to right communication. Scintigraphy showed normal excretion of Tc-99m IDA into the small intestine from the liver. Serum total bilirubin was 13.9mg/dl while direct bilirubin was 7.35mg/dl. Liver biopsy was done at 2 months old and revealed paucity of the interlobular bile ducts but no definite periportal fibrosis could be detected. Eye examination disclosed bilateral posterior ocular embryotoxon. MRI exhibited left pulmonary artery stenosis(Fig. 1), butterfly vertebra (Fig.2) and hepatomegaly. As a result of these symptoms Alagille Syndrome was diagnosed.


Fig. 1. T1-weighted coronal MR image shows left peripheral pulmonary artery stenosis. Fig. 2. T1-weighted coronal MR image shows butterfly vertebra of T6.


DISCUSSION
　Arteriohepatic dysplasia was first proposed by Watson and Miller in 1973 [1] while in 1975 Alagille gave a more detailed description of the syndrome[2]. Five common features of Alagille syndrome are: paucity of intrahepatic bile duct, characteristic facies, peripheral pulmonary artery hypoplasia or stenosis, vertebral arch defects and posterior ocular embryotoxon. Presence of at least three of the five main features can be considered as incomplete syndrome (including cholestasis)[3]. It is essential to differentiate syndromic from nonsyndromic cholestasis. This is especially critical in the case of extrahepatic biliary atresia in early infancy to avoid unnecessary surgery. The inheritance pattern is supposed to be autosomal dominant with variable penetrance. Locating siblings or parents with isolated anomalies of either the major or minor criteria strengthens this hypothesis[4]. Genetic counseling is difficult in view of the variable severity of both the liver disease and associated abnormalities. Scintigraphy with Tc-99m IDA demonstrates persistently retained radioactivity in the periphery of the liver while the central portion shows normal tracer clearance, resulting in a photopenic center surrounded by a hot peripheral rim on the later images. In addition, the gall bladder and small intestine promptly appear[5]. Treatment is mainly medical including early vitamin E supplementation in preventing or resolving the neurologic manifestations secondary to prolonged cholestasis[3]. Supplementation of vitamin D and calcium on a long term basis is also suggested to prevent fracture as a result of chronic cholestasis[6]. However in severe cases with periportal fibrosis, liver failure or dystonia resulting as a complication from manganese intoxication[7], a liver transplant might be needed. The long term prognosis depends on the severity and duration of the early cholestasis resulting in secondary malnutrition and infectious consequences in the youngest patients; severity of complex cardiovascular abnormalities leading to early death. Liver status leading to portal hypertension or liver failure is responsible for late deaths.
　MRI is the modality of choice for the evaluation of heart and great vessels other than echocardiogram while biopsy provides the definite diagnosis of paucity of interlobular bile ducts. Although Alagille stresses the easy recognition of the syndrome, in our admitted limited experience our opinion suggest that it is sometimes difficult to observe. We suggest further studying the cardiac condition in cases of infantile chronic cholestasis with vertebral anomaly for early detection of the syndrome.

REFERENCES
  1. Watson G. H., Miller V. Arteriohepatic dysplasia. Arch Dis Child 1973; 48: 459-466
  2. Alagille D, Odievre M., Gautier M., Dommergues J.P.. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur. J Pediatr 1975; 86:63-71
  3. Alagille D, Estrada A., Hadchouel M.,Gautier M., Odievre M., Dommergues J.P.. Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): Review of 80 cases. J Pediatr 1987; 110: 195-200
  4. Riely Caroline A., Labrecque Douglas R, Ghent Cameron, Horwich Arthur, Klatskin Gerald. A father and son with cholestasis and peripheral pulmonic stenosis: a distinct form of intrahepatic cholestasis. J Pediatr 1978; 92: 406-411
  5. Aburano Tamio, Yokoyama Kunihiko,Takayama Teruhiko, Tonami Norihisa, Hisada Kinichi. Distinct Hepatic Retention of Tc-99m IDA in Arteriohepatic Dysplasia (Alagille Syndrome). Clin Nucl Med 1989;14:874-876
  6. Lin Linen, Chang Mei-Hwei, Tsai Wen-Yu, Tsai Keh-Sung, Li Yiu-Wah. Bone fracture in children with chronic cholestasis. Acta Paediatrica Sinica 1997; 38: 360-364
  7. Devenyi Attila G, Barron Todd F.,Mamourian Alexander C.. Dystonia, Hyperintense Basal ganglia, and high whole blood manganese levels in Alagille Syndrome. Gastroenterology 1994; 106: 1068-1071

阿拉之症侯群：一病例報告
劉武翹　鄭慶明　李紋瑜　沈慶村1　王永成　吳昭瑩　孔慶惠
國泰綜合醫院　放射線科　小兒科1
　　阿拉之症侯群包含新生兒慢性膽汁鬱滯，肺動脈狹窄，蝴蝶狀椎体，特異臉形及眼 睛病變 。病理學上呈現肝內膽管數目減少為本症之特色。我們報告一名四歲大男孩，因持續黃疸入院。磁振影像顯示左側肺動脈週邊狹窄以及單一蝴蝶狀椎体，雙眼有胎生環，肝臟生檢呈肝內膽管數目減少為典形的阿拉之症侯群病例。

關鍵詞： 膽汁鬱滯；磁振影像；肺動脈狹窄
Received: February 25, 1998　　 Accepted: April 13, 1998
Correspondence to: Dr. Mo-Kiu Lau
Department of Radiology, Cathay General Hospital
280, Jen Ai Road, Section 4, Taipei. 106 Taiwan, R.O.C.