Naveh Y, Bassan L, Rosenthal E, Berkowitz D, Jaffe M, Mandel H, Berant M
Department of Pediatrics, Rambam Medical Center, Haifa, Israel.
J Pediatr Gastroenterol Nutr. 1997 May;24(5):548-54. doi: 10.1097/00005176-199705000-00011.
Progressive familial intrahepatic cholestasis, which constitutes a heterogeneous group of imperfectly delineated syndromes and appears to be inherited as an autosomal recessive condition, has not been hitherto reported from the Middle East, in spite of the high rate of consanguineous marriage in this region.
Sixteen affected children from six Israeli Arab families were evaluated over 30 years. All were born to consanguineous parents.
Jaundice appeared during the first 3 weeks of life in 15 babies. When first referred, 10 had hepatomegaly and nine had splenomegaly. A progression toward cirrhosis was the rule. Serum levels of conjugated bilirubin, liver enzymes, and alkaline phosphatase were raised; gamma-glutamyl transpeptidase levels were normal in all three infants in whom it was examined, but elevated in two siblings of another family at ages 2 and 3 years. No abnormal bile acids were detected in the serum and urine of patients. Histologic examination of the liver showed giant-cell transformation, paucity of intrahepatic bile ducts, cholestasis, fibrosis, or cirrhosis. The pattern of liver pathology differed at times among affected members within the same family. Therapeutic trials with phenobarbital, cholestyramine, or ursodeoxycholic acid were ineffective. Survival of the patients was from 5 to 18 months in four families; in the other two families, three children received liver transplants, and one is awaiting liver transplantation.
Progressive familial intrahepatic cholestasis should be included in the differential diagnosis of infants with cholestatic jaundice of unknown etiology, especially those born to consanguineous Arab parents.
进行性家族性肝内胆汁淤积症是一组尚未完全明确的异质性综合征，似乎以常染色体隐性遗传病形式遗传。尽管中东地区近亲结婚率很高，但此前该地区尚未有相关报道。
对来自6个以色列阿拉伯家庭的16名患病儿童进行了30年的评估。所有患儿均为近亲结婚的父母所生。
15名婴儿在出生后的前3周内出现黄疸。初诊时，10名患儿有肝肿大，9名有脾肿大。病情通常会发展为肝硬化。血清结合胆红素、肝酶和碱性磷酸酶水平升高；在接受检查的3名婴儿中，γ-谷氨酰转肽酶水平均正常，但在另一个家庭的2名2岁和3岁的兄弟姐妹中升高。患者血清和尿液中未检测到异常胆汁酸。肝脏组织学检查显示巨细胞转化、肝内胆管稀少、胆汁淤积、纤维化或肝硬化。同一家族中受影响成员的肝脏病理模式有时会有所不同。苯巴比妥、消胆胺或熊去氧胆酸的治疗试验均无效。4个家庭中患者的存活时间为5至18个月；在另外2个家庭中，3名儿童接受了肝移植，1名正在等待肝移植。
进行性家族性肝内胆汁淤积症应纳入病因不明的胆汁淤积性黄疸婴儿的鉴别诊断，尤其是近亲结婚的阿拉伯父母所生的婴儿。
