STUDY OF INHERITANCE IN PROGRESSIVE INTRA-HEPATIC CHOLESTASIS - HEPATIC EXCRETORY FUNCTION IN UNAFFECTED FAMILY MEMBERS

In an attempt to identify the heterozygotes state for progressive intrahepatic cholestasis (PIC), hepatic excretory function (131I rose bengal half-life (t½) and bromosulpthalein-transport maximum (BSP-Tm) was studied in controls and in eight members of a family, two of whom are affected with PIC. Values for131I rose bengal t½ varied over a wide range in normal controls and were normal in patients with the syndrome of cholestasis and peripheral pulmonic stenosis in whom BSP-Tm and 45 min % retention were abnormal.131I rose bengal t½ was abnormal in seven of eight family members. Despite this, BSP studies, including Tm, percent retention at 45 min, clearance were normal in all unaffected family members with the exception of the mother who has a reduced BSP-Tm. Fasting serum bile acid studies were normal in all unaffected family members. These studies do not clearly define the inheritance in this syndrome and suggest that any of the following three possibilities exist: 1) that the methods employed were not sensitive enough to detect heterozygotes, 2) that the inheritance in this syndrome is heterogenous; for instance, compound hetero- zygotes or autosomal dominant, or 3) that the family studies here represents a syndrome different from PIC. Speculation It has been suggested that the mode of inheritance of progressive intrahepatic cholestasis is autosomal recessive. The use of sensitive tests of hepatic excretory function (such as the t½131I rose bengal and the BSP-Tm may identify heterozygotes and confirm the type of inheritance. © 1979 International Pediatric Research Foundation, Inc.