Hunter’s syndrome

Primary lysosomal hydrolase defects. Two-thirds of the lysosomal storage diseases involve defects in genes that code for acid hydrolases. Table 41-2 lists 29 defects that have been defined so far. They have an autosomal recessive mode of inheritance, except for Hunter s syndrome and Fabry s disease, where the mode is X-linked recessive. The defective genes have been identified and mutations have been defined for nearly all. The nervous system is involved in most. Many of the disorders show a wide range of clinical severity, which may range from death in early childhood to a moderate disability in adulthood. 

Hunter s syndrome MPS 11 Iduronate sulfatase Dermatan sulfate Heparan sulfate... 

Frantatoni JC, Hall CW, Neufeld EF (1968) The defect in Hurler s and Hunter s syndromes faulty degradation of mucopolysaccharides. Proc Natl Acad Sci USA 60 699-706... 

Hunter s syndrome (type II) Initially, this disease was erroneously classified as type I-H. Its nosological independence and X-chromosomal recessive transmission were recognized in 1964 (A. Nja). The disease is based on a deficiency of L-iduron-sulphate sulphatase and sulphoiduronate sulphatase. The syndrome may appear in a moderate or severe form. 

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.]... 

Hunter s syndrome Dermatan sulfate Iduronate sulfohydrolase Brain, bone... 

Sjoberg, I., Fransson, L., Matalon, R., and Dorfman, A., Hunter s syndrome A deficiency of L-idurono-sulfate sulfatase. Biochem. Biophys. Res. Common. 54, 1125-1132 (1973). 

Sodium heparinate has been treated sequentially with methanolic hydrogen chloride and nitrous acid to produce 0-(methyl a-L-idopyranosyluronate 2-sulphate-(l -> 4)-2,5-anhydro-D-mannose. This disaccharide can be used for direct measurement of L-iduronic acid 2-sulphate sulphatase, an enzyme which is defective in Hunter s syndrome (mucopolysaccharidosis II). 

Several other trials are in progress and await completion and reporting of the data. Diseasesunder study include alphaj-antitrypsin deficiency, Fanconi s anemia, Gaucher s disease. Hunter s syndrome, Canavan s disease, limb girdle muscular dystrophy, amyotrophic lateral sclerosis, ornithine transcarbamylase deficiency, and junctional epidermolysis bullosa. 

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