The etiology of most cases of idiopathic
bile acid malabsorption (IBAM) is unknown. In this study, a Swedish family with
bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical
sodium-bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for several of the
nuclear receptors known to be important for ASBT expression: the farnesoid X receptor (FXR) and
peroxisome proliferator activated receptor alpha (
PPARalpha). The patients presented with a clinical history of idiopathic chronic watery
diarrhea, which was responsive to
cholestyramine treatment and consistent with IBAM.
Bile acid absorption was determined using (75)Se-homocholic
acid taurine (
SeHCAT);
bile acid synthesis was estimated by measuring the plasma levels of
7alpha-hydroxy-4-cholesten-3-one (C4). The ASBT, FXR, and
PPARalpha genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism (SSCP), denaturing HPLC, and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate with the
bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or
PPARalpha genes associated with the
bile acid malabsorption phenotype. These studies indicate that the intestinal
bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent
ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM.