Peptiduria Presumably Caused by Aminopeptidase-P Deficiency. A New Inborn Error of Metabolism

Abstract

Aminopeptidase-P (APP; EC 3.4.11.9) is an exopeptidase highly specific in cleaving the N-terminal imino bond in oligopeptides of an Xaa-Pro-sequence (Yaron and Berger, 1970). Active participation of APP in collagen metabolism, as well as a role in inactivation of biologically active peptides, has been proposed (Fleminger and Yaron, 1983); however its real biological function is still unknown. We report on a 5-month-old boy with epilepsy, and his healthy 5-year-old brother, both of whom were found to excrete massive quantities of imino-oligopeptides, amongst which Gly-Pro-4Hyp-Gly (GPOG) was the most prominent. With the exception of the tetrapeptide, all other peptides can also be detected in lower concentrations in the urines of healthy children. Specific GPOG-aminopeptidase activity in a small-intestinal biopsy of the healthy boy was absent or markedly decreased as compared with controls, while saccharase activity in the same biopsy was normal. An exogenous source of the tetrapeptide was excluded by a gelatin loading test. Because the enzyme system found in dog and human small intestine seems to be identical with APP we propose an APP deficiency in these brothers with and without clinical symptoms. This is, beside the defect of prolidase (EC 3.4.13.9) deficiency (Buist et al., 1972), the second known peptidase deficiency.