Primary bile acid malabsorption is an intestinal disorder associated with chronic watery diarrhea, excess fecal bile acids, and steatorrhea. Bile acid malabsorption has been classified into 3 main types depending on the etiology. Types 1 and 3 are ... Primary bile acid malabsorption is an intestinal disorder associated with chronic watery diarrhea, excess fecal bile acids, and steatorrhea. Bile acid malabsorption has been classified into 3 main types depending on the etiology. Types 1 and 3 are secondary disorders: type 1 is due to ileal dysfunction resulting from Crohn disease or ileal resection, and type 3 is secondary to other conditions, including cholecystectomy, post-vagotomy, celiac disease, and pancreatic insufficiency. Type 2 bile acid malabsorption is a primary congenital disorder, including the rare type due to mutations in the SLC10A2 gene (review by Pattni and Walters, 2009).
Hess Thaysen and Pedersen (1976) described several patients who had chronic lifelong watery diarrhea and excessive bile acid loss, without other ileal pathology. The diarrhea resolved upon bile acid sequestration with cholestyramine.
Heubi et al. (1979, ... Hess Thaysen and Pedersen (1976) described several patients who had chronic lifelong watery diarrhea and excessive bile acid loss, without other ileal pathology. The diarrhea resolved upon bile acid sequestration with cholestyramine. Heubi et al. (1979, 1982) reported a case study of a boy who presented 48 hours after birth with severe diarrhea, steatorrhea, and malabsorption, requiring parenteral nutrition. Intestinal absorption of bile acid was nearly absent and resulted in a small bile acid pool size, a low interluminal bile acid concentration, and severe malabsorption of water and fat. Ileal biopsies showed no active bile acid transport. The findings were consistent with a congenital transport defect that includes absence of active ileal bile acid transport presenting as diarrhea in infancy. In a follow-up of this patient, Oelkers et al. (1997) stated that he had consistently low plasma LDL cholesterol levels and no family history of the disorder. Heubi et al. (1982) described an apparent familial defect in active ileal bile acid transport. At the other extreme, a child with marked bile acid malabsorption but with almost normal growth and development, nearly normal fat absorption, and a moderately well-maintained bile acid pool, was described by Jonas et al. (1986). This patient had a 15-fold increase in bile acid synthesis that was adequate to maintain pool size, interluminal bile acids, and fat absorption. This report indicated that the clinical phenotype apparently can vary from severe diarrhea, fat malabsorption, and malnutrition, to modest diarrhea without significant fat malabsorption. In a review, Small (1997) suggested that the bile acid malabsorption and the variable severity could represent mutations in any of the main players involved in ileal bile transport.
Small et al. (1972) suggested that a genetic defect in the predicted bile acid receptor in the ileum would lead to diarrhea and/or steatorrhea and suggested that bile acid turnover and fecal bile acid excretion be studied in ... Small et al. (1972) suggested that a genetic defect in the predicted bile acid receptor in the ileum would lead to diarrhea and/or steatorrhea and suggested that bile acid turnover and fecal bile acid excretion be studied in patients with unexplained diarrhea. In the patient with PBAM reported by Heubi et al. (1979, 1982), Oelkers et al. (1997) identified compound heterozygosity for 2 mutant SLC10A2 alleles (601295.0001 and 601295.0002). In vitro functional expression assays in transfected COS cells showed that the mutant proteins had abolished transport activity for conjugated bile acids. The findings of Oelkers et al. (1997) established that SLC10A2 mutations can cause PBAM and underscored the role of the ileal sodium/bile acid cotransporter in intestinal reclamation of bile acids. The patient's unaffected son was heterozygous for 1 of the alleles, consistent with autosomal recessive inheritance.