Enzyme-replacement Therapy in Mucopolysaccharidoses with a Specific Focus on MPS VI

Before the discovery of the lysosome, already three out of the seven currently known mucopolysaccharidoses (MPSs) were described in medical literature. In 1917, Hunter syndrome was the first to be described in two brothers (“they are as alike as two peas”) by Charles Hunter. Gertrud Hurler published her two case reports about MPS I in 1919, and MPS IV was outlined in 1929 by the Uruguayan dr. Morquio. All described young children with or without mental impairment, with profound bone abnormalities. In 1955, the Belgian scientist Christian de Duve discovered a new intra-cellular organelle that he named the lysosome. Eventually, this brought light to more than 50 inherited diseases all concerning a defect in the lysosomal system. The group of mucopolysaccharidoses belonged to these lysosomal disorders and all types proved to be characterized by the deficiency of a lysosomal enzyme. New types of MPSs were discovered since then. In 1963 two French physicians described a new form of dysostosis mupltiplex, MPS VI, and the syndrome was named after them: Maroteaux-Lamy’s syndrome 4. In the same year dr. Sanfilippo described for the first time a MPS III patient with mental impairment and excretion of heparan sulphate. Later, Sanfillippo disease was subdivided in type A, B, C, and D because between 1972 and 1980 different enzyme deficiencies were discovered in each of the four subtypes. Finally, in 1973, MPS VII was described by the American dr. Sly . MPS V and MPS VIII, first thought to be novel diseases, later turned out to be already known types of MPS and are not separate entities anymore. In 1996 Natowicz et al reported the first patient with MPS IX . Till now, only one other family has been reported with this disease.