PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS AMONG THE ARAB POPULATION IN ISRAEL

Background: Progressive familial intrahepatic cholestasis, which const itutes a heterogeneous group of imperfectly delineated syndromes and a ppears to be inherited as an autosomal recessive condition, has not be en hitherto reported from the Middle East, in spite of the high rate o f consanguineous marriage in this region. Methods: Sixteen affected ch ildren from six Israeli Arab families were evaluated over 30 years. Al l were born to consanguineous parents. Results: Jaundice appeared duri ng the first 3 weeks of life in 15 babies. When first referred, 10 had hepatomegaly and nine had splenomegaly. A progression toward cirrhosi s was the rule. Serum levels of conjugated bilirubin, liver enzymes, a nd alkaline phosphatase were raised; gamma-glutamyl transpeptidase lev els were normal in all three infants in whom it was examined, but elev ated in two siblings of another family at ages 2 and 3 years. No abnor mal bile acids were detected in the serum and urine of patients, Histo logic examination of the liver showed giant-cell transformation, pauci ty of intrahepatic bile duets, cholestasis, fibrosis, or cirrhosis, Th e pattern of liver pathology differed at times among affected members within the same family. Therapeutic trials with phenobarbital, cholest yramine, or ursodeoxycholic acid were ineffective. Survival of the pat ients was from 5 to 18 months in four families; in the Ether two famil ies, three children received liver transplants, and one is awaiting li ver transplantation. Conclusions: Progressive familial intrahepatic ch olestasis should be included in the differential diagnosis of infants with cholestatic jaundice of unknown etiology, especially those born t o consanguineous Arab parents.