Carbohydrate-deficient glycoprotein syndrome is group of disorders that present in infancy with failure to thrive, multiple organ system involvement and severe neurologic manifestations. The underlying metabolic defects are in the multi-step, complex synthesis of N-linked oligosaccharides, distinct multisugar structures that have important biologic functions. One enzyme, phosphomannomutase, has been hypothesized to be deficient for some CDGS patients. The biochemical characterization of phosphomannomutase (PMM) via the development of a new enzyme assay has elucidated the complexity of this particular metabolic defect. Molecular biologic techniques have revealed that American CDGS patients have both previously reported and novel base changes. The reported gene and its surrounding sequence is being analyzed. The remarkable clinical heterogeneity of the American CDGS population is being studied. Two American Type 4 CDGS patients have recently been identified, which doubles the world population. Biochemical studies on skin fibroblasts and lymphoblasts from these patients are being used to explore the synthesis of N-linked oligosaccharides in these Type 4 children. The clinical, molecular and biochemical characterization of CDGS provides insight into the important role of N-linked oligosaccharides in human physiology.
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