Mucopolysaccharidosis type I, II, IIIA and V. Pathological and biochemical abnormalities in the neural and mesenchymal elements of the brain.

Histochemical and electron microscopic studies of the brains inclusive of the leptomeninges containing large blood vessels from 7 patients with mucopolysaccharidosis (MPS) I, II, IIIA and V showed marked increase in mesenchymal elements and the generalized presence of characteristic lesions around cerebral veins and arteries. The periadventitial space was greatly distended and filled with viscous fluid and numerous mononuclear cells containing large cytoplasmic vacuoles; these cells stained positively for glycosaminoglycans (GAG). In contrast, the neurons showed only a slight increase of GAG over the normal controls but contained an excessive amount of glycolipid-like material. The amount of GAG in the leptomeninges, inclusive of the large blood vessels, was 10.8, 6.5, 4.5 and 2.2 times greater in patients with MPS I, II, V and IIIA respectively, than the mean of unaffected controls. Dermatan sulfate (DS) accounted for most of the GAG increase in MPS I, II and V [mixed excretors of DS and heparan sulfate (HS)], and HS for the GAG increase in MPS IIIA (HS excretor). With the exception of the patient with MPS IIIA, whose GAG content and composition were the same in both the neural and mesenchymal elements, in all the other MPS types the mesenchymal elements contained more GAG, with a preponderance of DS. We conclude that the mesenchymal elements contribute substantially to the increased content of GAG in the brain and its coverings, mostly in the form of dermatan sulfate.