The mucopolysaccharidoses: a synergism between clinical and basic investigation

The mucopolysaccharidoses are a family of genetic diseases involving faulty degradation of one or more type of mucopolysaccharide or glycosaminoglycan. These conditions are characterized by skeletal, connective tissue, and intellectual manifestations. Biochemical investigations over the past 10-20 yr have enhanced our understanding of the clinical conditions and advanced our knowledge of catabolic pathways for complex biological structures. Identification of stored and excreted materials as partially degraded glycosaminoglycans allowed classification of these conditions on clinical and chemical criteria. The development of a cell culture model for studying the mucopolysaccharidoses lead to the identification of a variety of lysosomal sulfatases and glycosidases as deficient enzymes. This stimulated the identification of several new conditions. Knowledge of primary biochemical defects improved genetic services by providing accurate diagnosis, facilitating carrier identification and improving prenatal diagnosis. Glycosaminoglycan excretion patterns associated with individual enzyme defects suggested sequential degradative pathways for GAGs and related macromolecules. Attempts at enzyme replacement revealed a complex system of recognition markers and membrane receptors for the uptake of extracellular proteins. Multiple enzyme deficiencies are providing information on lysosomal enzyme synthesis and processing. The mucopolysaccharide storage diseases offer an excellent example of a productive synergism between basic biology and clinical medicine.