Glycopeptide storage in skin fibroblasts cultured from a patient with α mannosidase deficiency

Patients with mannosidosis, an inherited deficiency of lysosomal α mannosidase, accumulate large amounts of mannose rich oligosaccharides (the 'core' of the carbohydrate units of many glycoproteins) in brain and liver and excrete these partial degradation products in their urine. A profound α mannosidase deficiency was demonstrated in fibroblasts cultured from a skin biopsy obtained from a child with mannosidosis. Further, abnormal glycopeptides rich in mannose and similar to oligosaccharides found in the patient's urine were isolated from fibroblast extracts by a variety of chromatographic procedures and by virtue of their binding to a concanavalin A Sepharose 4B affinity column. This storage material contained mannose, N acetylglucosamine, and asparagine in the ratio 3:1:1 together with a few other amino acids and had a molecular weight of approximately 1,100. There was no evidence for excretion of storage material by mannosidosis fibroblasts or for any abnormality in cell surface glycoprotein composition. The glycopeptide nature of the storage material isolated from cultured skin fibroblasts may be attributed to the low level of N aspartyl β glucosaminidase (EC 3.5.1.-) activity in these cells.