Hydrocephalus, corneal opacities, deafness, valvular heart disease, deformed toes and leptomeningeal fibrous thickening in adult siblings: a new syndrome associated with-glucocerebrosidase deficiency and a mosaic population of storage cells

Abstract

We describe three adult siblings with communicating hydrocephalus, corneal opacities, deafness, valvular heart disease, and deformed toes associated with glucosylceramide (glc-cer)-β-glucosidase deficiency. The common manifestations of Gaucher disease were not evident. Supranuclear gaze palsies characteristic of type 3 were noted from early childhood, although the major signs were undeveloped until early adult life. Autopsy disclosed thickened leptomeninges with perivascular fibrosis, non-rheumatic calcified aortic and mitral stenosis with marked fibrosis, and mild infiltration of Gaucher cells in the reticuloendothelial organs. In contrast to the slight accumulation of glc-cer in the liver and spleen, the activity of glc-cer-β-glucosidase was markedly decreased in the tissues, as much as in a patient with type 2 Gaucher disease. Common mutations were not found in the glucocerebrosidase gene.