Hurler disease Mucopolysaccharidosis

First described in 1919 by Hurler, mucopolysaccharidosis I (MPS I, the Hurler syndrome) leads to accumulation of partially degraded dermatan and heparan sulfates (Fig. 4-11).317,352 353 A standard procedure in the study of diseases of this type is to culture fibroblasts from a skin biopsy. Such cells cultured from patients with the Hurler syndrome accumulate the polysaccharide, but when fibroblasts from a normal person are cultured in the same vessel the defect is "corrected." It was shown that a protein secreted by the normal fibroblasts is taken up by the defective fibroblasts, permitting them to complete the degradation of the stored polysaccharide. 

Mucopolysaccharidosis I (Hurler, Hurler-Scheie and Scheie syndromes) a-L-Iduronidase HS, DS Short stature, skeletal dysplasia, coarse facial features, joint stiffness, visceromegaly, cardiac disease, comeal clouding, CNS involvement... 

Stepwise degradation of heparan sulfate. The deficiency disea.ses corresponding to the numbered reactions are I = mucopolysaccharidosis (MPS) II, Hunter s syndrome 2 = MPS I, Hurler s, Scheie s, and Hurler-Scheie s syndromes 3 = MPS III A, Sanfilippo s syndrome type A 4 = MPS III C, Sanfilippo s syndrome type C 5 = MPS 111 B, Sanfilippo s syndrome type B 6 = no deficiency disease yet known 7 = MPS VII, Sly s syndrome 8 = MPS III D, Sanfilippo s syndrome type D. The schematic drawing depicts all structures known to occur within heparan sulfate and does not imply that they occur stoichiometrically. Very few of the glucuronic acid residues are sulfated. [Reproduced with permission from E. F. Neufeld and J. Muenzer. In Metabolic Basis of Inherited Disease, 7th ed., C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle (Eds). McGraw-Hill, New York, 1995, p. 2468.]... 

Studies using different methods of harvesting cultured human fibroblasts from a patient exhibiting mucopolysaccharidosis, and amniotic fluid, have indicated that reliable prenatal diagnosis of mucopolysaccharidosis can be performed only if the pericellular pool of glycosaminoglycans is removed by pretreatment with trypsin. Thus amniotic fluid cells from a pregnancy carrying a foetus affected by Hurler s disease revealed the expected increase in the level of S04-incorporation into fibroblasts only after mild proteolytic treatment. 

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