Disturbed metabolism of copper and zinc in aspartylglycosaminuria: Possible involvement with connective tissue changes

Abstract

In aspartylglycosaminuria (AGU), a lysosomal storage disorder of glycoprotein degradation, there are some abnormalities in collagen and proteoglycan metabolism. Because of earlier observations suggesting a disturbance of copper balance, the metabolism of copper and zinc was studied in more detail to find out if possible trace metal disturbances could be correlated with connective tissue disorder. Highly elevated copper concentrations in the hair and significantly reduced zinc levels in serum and urine were detected in AGU patients indicating a disturbance of trace element balance. However, the patients had normal serum copper levels, and the concentrations of zinc and copper in cultured fibroblasts did not differ from those of control cells. Normal lysyl oxidase activities in cell culture indicate that collagen cross-link formation is not affected. The changes in copper and zinc balance are probably secondary to the basic enzyme deficiency, and may contribute to the development of the clinical signs and symptoms of AGU although the mechanisms involved are not yet understood.

Secondary biochemical and morphological consequences in lysosomal storage diseases

“…These observations were highlighted by the marked reduction of mRNA levels of biglycan and several fold increase in mRNA levels of decorin in fibro blasts of patients with aspartylglucosaminuria [122]. It is noteworthy that both biglycan and decorin are important protein components of collagen fibril associated proteo glycans affecting copper and zinc metabolism [123].…”