Mucopolysaccharidosis IV (Morquio Syndrome)

Morquio syndrome (mucopolysaccharidosis IV: MPS IV) is an autosomal recessive disease classified in the group of mucopolysaccharide storage diseases. Two forms are recognized, type A and type B. MPS IVA is characterized by the absence of the enzyme N-acetylgalactosamine 6-sulfate sulfatase (GALNS). MPS IVB results from deficiency of the enzyme β-galactosidase. Both types excrete keratan sulfate (KS) in urine. In 1929, Morquio, a pediatrician in Uruguay, described cases of Morquio syndrome. In 1952, Brante isolated the stored mucopolysaccharides in Morquio patients. In 1976, the enzyme deficiency in MPS IVA (GALNS deficiency) was identified (Singh et al. 1976). Shortly thereafter, the enzyme deficiency in MPS IVB was described (β-galactosidase deficiency). Historically, MPS IVA was considered to have more severe manifestations than MPS IVB. However, with the ability to differentiate between types A and B by enzyme analysis, variability in clinical expression in both groups becomes apparent. Recently, three different MPS IVA mice models have been established (Tomatsu et al., 2003b; unpublished data). Clinical manifestations in the affected mice are milder than those in human patients. Only palliative measures are currently available for treatment of patients with MPS IV. Potential strategies, currently at different levels of development, include enzyme replacement, gene therapy, and allogenic bone marrow transplantation in which engrafted cells provide the normal enzyme. Those treatments are expected to enable dramatic improvements in visceral organs but little or no improvements in bone because the enzymes are not delivered to the bone effectively. In this context, the challenge still is to maximize the clinical efficacy to the bones, especially to systematic bone disease, MPS IV. In this chapter, we review the clinical manifestations, incidence, diagnosis, and treatments for MPS IV, mainly focusing on IVA.