Pathophysiologic and ultrastructural basis for intestinal symptoms in Fabry's disease.

Fabry's disease is a rare, sex-linked disorder of glycolipid metabolism. We describe a patient with watery diarrhea, early satiety, and asymptomatic cholelithiasis. The jejunal aspirate demonstrated bacterial overgrowth; sigmoidoscopy showed rectal angiokeratoma corpora diffusum. The gastric emptying rate measured with 99mTc-sulfur colloid was markedly prolonged and the fasting gastrin was elevated at 276 pg/ml. The (14C)glycocholate breath test demonstrated a markedly elevated peak at 4 h, associated with an increased fecal bile acid loss of 0.82 g/day. Oral cholecystogram showed a solitary radiolucent stone in a functioning gallbladder. The bile acid pool size and lithogenic index were normal. Light microscopy of small bowel and rectal biopsy specimens revealed normal surface epithelium, but enlarged and vacuolated ganglion cells in Meissner's plexus. Electron microscopy showed laminated and amorphous osmiophilic deposits within ganglion cells of the submucosal plexus, within smooth muscle cells of the muscularis mucosae, and within endothelial cells lining arterioles, venules, and capillaries, but not in autonomic nerve fibers or enterocytes. The diarrhea and early satiety responded promptly to metoclopramide and to tetracycline. The early satiety was likely on the basis of delayed gastric emptying due to deposition of sphingolipid within ganglion cells of the autonomic nervous system; the diarrhea was likely on the basis of intestinal stasis with bacterial overgrowth and bile salt wastage.