Studies of Intestinal Transport Defect in Hartnup Disease

Abstract

Hartnup disease was discovered in two brothers as a result of a survey for amino acid disorders. Two unaffected brothers and a series of control subjects were also studied. Intestinal amino acid transport was measured by in vivo and in vitro techniques. In the affected brothers tryptophan and phenylalanine transport were defective, methionine transport was abnormal in one of the two, and leucine, lysine, and proline transport were normal in vivo. The transport of methionine and tryptophan by mucosal segments in vitro was markedly reduced in the affected brothers in whom these studies were performed. In both affected brothers transport of lysine and glycine in vitro was minimally reduced and correlated with modest increases of these amino acids in the urine. Measurements of stool indoles and urine indican revealed elevation in both brothers after oral tryptophan loading. The defect in neutral amino acid transport seen in the intestine in Hartnup disease is demonstrable in vitro. Further studies are required to correlate transport in vitro, with absorption in vivo and with the aminoaciduria.