Abnormal Dermal Proteoglycan in Aspartylglycosaminuria: A Possible Mechanism for Ultrastructural Changes of Collagen Fibrils in a Glycoprotein Storage Disorder

Abstract

Changes in the structure and organization of collagen fibrils were recently described in the skin of aspartylglycosaminuria patients. The skin of the patients contained a normal amount and distribution of glycosaminoglycans, but the dermatan sulfate of aspartylglycosaminuria skin was more sensitive to chondroitinase AC digestion, resulting in unsaturated 4-sulfated disaccharides which were not detected in controls. Isolated dermatan sulfate chains as well as the chains present in the intact core protein synthesized by skin fibroblasts from an aspartylglycosaminuria patient were also digestible with chondroitinase AC, while those of a control fibroblast culture could be digested with chondroitinase ABC only. This is indirect evidence for abnormal epimerization of dermatan sulfate in the skin of aspartylglycosaminuria patients, which may be associated with the changes in collagen fibril formation.

Retarded bone formation in GM1-gangliosidosis: a study of the infantile form and comparison with two canine models

“…Similar interaction between proteoglycans and collagen was described in the skin of patients with aspartylglycosaminuria [21,22]. Structural changes of collagen were attributed to abnormal proteoglycan in aspartylglycosaminuria, a lysosomal disease with storage of partially degraded N-linked oligosaccharides [21,22]. A similar abnormality of collagen might lead to loss of firmness of cartilage resulting in focal necrosis as seen in the vertebrae of our 9-month-old affected puppies and a cat with MPS-VI [1,26].…”

“…It is well documented that small proteoglycans may inhibit the fibrillogenesis of type II collagen [35], which is the major collagen of cartilage [19]. Similar interaction between proteoglycans and collagen was described in the skin of patients with aspartylglycosaminuria [21,22]. Structural changes of collagen were attributed to abnormal proteoglycan in aspartylglycosaminuria, a lysosomal disease with storage of partially degraded N-linked oligosaccharides [21,22].…”

Altered Corneal Stromal Matrix Organization is Associated with Mucopolysaccharidosis I, III and VI

“…The primary changes are the consequence of the abnormal accumulation of substrates or catabolites that lead to severe impairment of cellular structure and function (Herschkowitz and Schulte, 1984). The secondary changes are likely due to disrupted recycling and are manifested in abnormal synthesis of cellular and extracellular elements (Nanto-Salonen, 1984, 1987Lovell, 1990 ;Kaye et al, 1992 ;Holleran et al, 1994 ;Maatta et al, 1994 ;Pitto et al, 1996).…”

Extracellular matrix components: An intricate network of possible biomarkers for lysosomal storage disorders?

“…This increased versican expression was hypothesized to be a potential disease causing mechanism, especially concerning the CNS involvement of the disorder, due to possible defects in cell to cell interactions and intracellular organization resulting from the specific PG differential expression. In aspartyglucosaminuria an alteration in the epimerization of PGs [110], in combination with a reduction in the synthesis of biglycan and an increase in the production of decorin, were identified [111]. This differential expression of PGs was hypothesized as the possible causative mechanism for the observed alterations in the skin collagen fiber expression and arrangement [110,111].…”