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Pathophysiology of diarrhea in patients with familial amyloid neuropathy.

Seven patients with familial amyloid neuropathy (AF amyloidosis) were studied to clarify the pathophysiology of the diarrhea associated with this disorder. Fecal weight and fat determinations, 14C-glycocholate breath tests, and a test of B12 absorption were performed before and after treatment with co-trimoxazole. Gastric emptying was assessed with conventional roentgen contrast medium and radio-opaque markers. Gastric emptying was delayed, fecal weight and fat excretion increased, and the 14C-glycholate breath test abnormal in all but one patient. In most cases co-trimoxazole reduced diarrhea, steatorrhea, and 14C-glycine deconjugation; vitamin B12 absorption returned to normal in one patient after co-trimoxazole treatment. In a jejunal mucosal biopsy specimen, amyloid was absent in the villi, but small deposits were detected along small vessels and nerves in the lamina propria. These findings suggest altered gastrointestinal motility due probably to an autonomic neuropathy which in turn leads to enteral bacterial overgrowth and subsequently to diarrhea and steatorrhea. This diarrhea can be temporarily alleviated by co-trimoxazole treatment.