Benign recurrent intrahepatic cholestasis is characterized by intermittent episodes of cholestasis without extrahepatic bile duct obstruction. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months ... Benign recurrent intrahepatic cholestasis is characterized by intermittent episodes of cholestasis without extrahepatic bile duct obstruction. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months (Summerskill and Walshe, 1959; Schapiro and Isselbacher, 1963; Brenard et al., 1989). Tygstrup et al. (1999) stated that referring to this disorder as 'benign' is a misnomer, because the disease has an impact on the quality of life in some patients. They preferred the term 'recurrent familial intrahepatic cholestasis.' - Genetic Heterogeneity of Benign Recurrent Intrahepatic Cholestasis See also BRIC2 (605479), caused by mutation in the ABCB11 gene (603201) on chromosome 2q24.
Summerskill and Walshe (1959) reported 2 unrelated patients with recurrent intrahepatic cholestasis. Kuhn (1963) described 2 teenaged brothers who had repeated attacks of jaundice accompanied by itching and hepatomegaly. Progression to biliary cirrhosis was suspected in one. ... Summerskill and Walshe (1959) reported 2 unrelated patients with recurrent intrahepatic cholestasis. Kuhn (1963) described 2 teenaged brothers who had repeated attacks of jaundice accompanied by itching and hepatomegaly. Progression to biliary cirrhosis was suspected in one. Tygstrup (1960) described the condition in 2 distantly related 15-year-old boys living in a small village in the Faroe Islands. Onset in these patients was in the first 2 years of life. Cholestasis was demonstrated by liver biopsy and direct cholangiography. Tygstrup and Jensen (1969) described intermittent intrahepatic cholestasis in 5 young males from the Faroe Islands. The disorder was characterized by recurrent attacks of pruritus and jaundice. During disease-free intervals, which lasted for months or years, no clinical or biochemical indication of cholestasis was found. Tygstrup et al. (1999) reported a follow-up 30 years later on the 5 patients in the original report and described 5 additional patients from the Faroe Islands. Progression to chronic liver disease had not occurred. The episodes of cholestasis tended to reduce in frequency with age. The youngest patient, aged 25 years, who had had 16 episodes lasting about 6 months each, had a liver transplant after which no further episodes were recorded 1 year after surgery. Minuk and Shaffer (1987) studied a man who developed severe pruritus followed by jaundice and thereafter had 5 episodes, each of 3 or 4 months' duration, during the next 8 years. A brother and sister also had episodes of pruritus followed by jaundice. De Koning et al. (1995) provided full pedigree and clinical information on a large kindred with BRIC reported by Houwen et al. (1994). Four patients in 3 distantly related sibships, all with consanguineous parents, were described. Affected children first developed pruritus and icterus at ages ranging from 2 to 8 months. Cholestatic jaundice disappeared clinically and biochemically after 6 to 9 months, but subsequent episodes occurred. None of the obligatory carriers of the BRIC gene experienced signs of the disease. Four patients observed were from a population estimated to number 10,000 descended from the inhabitants of a small village founded in the middle ages, indicating a high carrier frequency.
In patients with BRIC1, Bull et al. (1998) identified mutations in the ATP8B1 gene (602397.0006; 602397.0007). Most had homozygous or compound heterozygous mutations; some only had a heterozygous mutation.
In the patients with BRIC from the ... In patients with BRIC1, Bull et al. (1998) identified mutations in the ATP8B1 gene (602397.0006; 602397.0007). Most had homozygous or compound heterozygous mutations; some only had a heterozygous mutation. In the patients with BRIC from the Faroe Islands originally reported by Tygstrup (1960), Tygstrup et al. (1999) identified a founder mutation in the ATP8B1 gene (I661T; 602397.0006).