Mucopolysaccharidosis types I, II, IIIA and V

Abstract

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.

Growth patterns for untreated individuals with MPS I: Report from the international MPS I registry

“…An initial report of a brain necropsy in MPS I identified swelling of most of the large cerebral cortical neurons with increased numbers of astrocytes, numerous perivascular aggregations of fibrous astrocytes throughout gray matter, and greatly enlarged perivascular spaces in the white matter filled with collagen and microglial phagocytes (Bishton, Norman, & Tingey, 1956). Brain assessments in MPS disorders also demonstrated a mesenchymal contribution to increased brain size that is due to mononuclear cells filled with GAGs in distended periadventitial spaces, GAG accumulation in leptomeninges, and, instead of GAGs, the neurons contained an excessive amount of glycolipid-like material (Dekaban & Constantopoulos, 1977) shown to be an accumulation of sphingolipids (Constantopoulos & Dekaban, 1978;Kreutz et al, 2013).…”

Glycosaminoglycan storage in neuroanatomical regions of mucopolysaccharidosis I dogs following intrathecal recombinant human iduronidase

“…Glycosaminoglycans (GAG) accumulate in MPS disease, but these substances do not appear to be directly neurotoxic. Secondary accumulation of GM2 and GM3 gangliosides occurs, and these are the major stored material in brain neurons (1, 2). Gangliosides may cause dendritic sprouting (3).…”

Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases

“…Although little is known about early disease development, MPS III mainly affects the neurons of the central nervous system causing dementia, mental retardation, delayed development, and neurological dysfunction (157,238,239). Typical neuropathological lesions include loss or ballooning of purkinje cells and accumulation of molecular layer dendrites with storage material (157,(240)(241)(242). Death usually occurs in the patient's early twenties to early thirties, for patients with the severe form, while patients suffering from the attenuated form have longer survival times (243)(244)(245).…”