[Congenital disorders of glycosylation. Their diagnosis and treatment]

Glycosylation disorders are alterations in the biosynthesis of either N-glycoproteins, O-glycoproteins or both. Most of these diseases are multisystemic and lead to severe psychomotor retardation. Since Jaeken reported the first disorder in the N-glycosylation of proteins in the 1980s, our knowledge of clinical glycobiology has increased considerably. Thus, glycosylation disorders now include specific tissue diseases, such as disorders affecting cellular signalling that give rise to anomalous cell growth (cancer), disorders of leukocyte traffic and congenital muscular dystrophies associated to alterations in neuronal migration. All these diseases are the result of the presence of very specific anomalous glycans, which are often difficult to detect in physiological fluids and for which new diagnostic tools have to be developed.

In this review, first, we outline the two most frequent routes for the glycosylation of proteins in humans, followed by a brief description of the associated genetic diseases and the diagnostic tools and therapies that are currently available.

Every year new disorders are detected in the N- and O-glycosylation routes, and due to the fact that there are an estimated 500 genes involved in the synthesis or the functioning of glycoproteins, it would seem that, taken together, those that are currently known may well be just the 'tip of the iceberg'.