Lysosomes and the sclerotic arterial lesion in Hurler's disease

A case of Hurler's disease in a mentally retarded, six year old boy is reported. In Hurler's disease a lysosomal hydrolase, l-iduronidase, is deficient, and consequently undegradable mucopolysaccharide accumulates within lysosomes in many tissues. Severe occlusive coronary artery disease and sclerotic aortic lesions are common in very young patients, although their serum lipid and blood pressure levels are normal. Vascular collagen and elastin is increased, but little or no stainable lipid is present. Electron microscopy shows that aortic smooth muscle cells are distended by vacuoles, appearing empty in formalin fixed tissues, that identify them as the "gargoyle" cells in the proliferative lesion. The presence of a basic lysosomal defect and the absence of other contributing metabolic factors suggest that accumulation of an excess of undegradable substrate within smooth muscle lysosomes may be an initiating event in the development of proliferative sclerotic vascular lesions.