Digestive Tract and Renal Small Vessel Hyalinosis, Idiopathic Nonarteriosclerotic Intracerebral Calcifications, Retinal Ischemic Syndrome, and Phenotypic Abnormalities

Abstract A new familial syndrome that affected 3 of 7 siblings is described. All 3 patients were young women with a very peculiar phenotype, poikilodermia and hair greying, and idiopathic nonarteriosclerotic cerebral calcifications. Pathological studies demonstrated a marked and progressive hyalinosis involving capillaries and often arterioles and small veins of the digestive tract, kidneys, and calcified areas of the brain. Using electron microscopy, we found that the hyalin substance in the intestinal capillaries consisted of several concentric layers of basal membrane-like deposits within a finely granular fluffy material. Huge deposits of this material were present in the subepithelial and mesangial spaces of the kidneys. Endothelial cells and, in the kidneys, mesangial cells were markedly abnormal, and a true mesangiolysis pattern was present in 2 patients. The clinical and biologic expression of these vascular changes was variable. Diarrhea, rectal bleeding, malabsorption, and protein-losing enteropathy were the main and lethal clinical problems in the proband. Hypertension appeared in the early stage of a second pregnancy in 1 sister, and mild proteinuria was found in all 3 affected patients. Peripheral retinal ischemic syndrome and chorioretinal scars were found in the ocular fundi of both affected sisters of the proband. A subarachnoid hemorrhage, due to a right sylvian aneurism, also occurred in both sisters and was lethal in 1 sister. None of the known causes of distal vessel hyalinosis could be ascertained.