INHERITED DISORDERS OF GLYCOPROTEIN-SYNTHESIS - CELL BIOLOGICAL INSIGHTS

Disorders of glycoprotein synthesis have been described only recently, and few have been studied extensively at both the clinical and bioche mical level, The identification and characterization of these rare dis eases are important, not only for the patients and their families, but because they offer enormous insight into biological processes, For ex ample, the targeting of acid hydrolases to lysosomes by mannose-6-phos phate was discovered as a direct result of the elucidation of the defe ct in I-cell disease, The notion of carbohydrates as targeting agents continues to have ramifications today, with the success of macrophage- targeted enzyme replacement therapy for Gaucher disease, Likewise, con firmation of the in vivo role of fucose containing glycans and selecti ns in neutrophil function came from studies using specimens from patie nts with leucocyte adhesion deficiency type II due to reduced availabi lity of GDP-fucose. Identification of the in vivo ligands of selectins also has implications for anti-inflammatory therapies, Macular cornea l dystrophy and spondyloepiphyseal dysplasia tarda offer an opportunit y to investigate the number of different sulfotransferases in cells, t heir substrates, and their tissue expression, The Ehlers-Danlos proger oid variant offers insight into the function and regulation of the pro teoglycan decorin, and suggests that several of the enzymes involved i n proteoglycan synthesis may function as a multienzyme complex, The co mmon occurrence of hypergonadotropic hypogonadism in patients with gal actosemia or carbohydrate-deficient glycoprotein syndrome, due to defe ctive N-linked glycosylation, suggests that ovarian function is partic ularly dependent on proper glycan synthesis, A host of other concepts await discovery as a fuller contingent of human disorders of glycan sy nthesis achieves recognition.