Sanfilippo’s syndrome

Haemophilia Hypercholesterinaemia Hyperlipoproteinaemia II Niemann-Pick disease Oxalosis Porphyria Reye s disease Sanfilippo s syndrome Sickle cell anaemia Thalassaemia (P)... 

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.]... 

Sanfilippo s syndrome Heparan sulfate Heparan sulfate N-sulfohydrolase Brain, bone... 

A marked increase in arylsulfohydrolase B activity is also observed in Hurler s syndrome and Sanfilippo s syndrome (Farooqui and Bachhawat, 1971 Farooqui and Mandel, 1977), which are characterized by a general alteration in glycosaminoglycan metabolism. The significance of these observations in relation to glycosaminoglycan metabolism is not understood at... 

Sanfilippo s syndrome is an inherited genetic disorder of heparan sulfate catabolism, characterized by progressive mental retardation, mild skeletal deformities, and excretion of excessive amounts of heparan sulfate in the urine (Dorfman and Matalon, 1976 McKusick, 1972). A deficiency of heparan sulfiite N-sulfohydrolase is responsible for the pathogenesis of Sanfilippo s syndrome (type A) (Kresse and Neufeld, 1972 Kresse, 1973 Hop-wood and Elliott, 1981). The patients and heterozygotes are diagnosed by estimating heparan sulfate N-sulfohydrolase activity in fibroblasts and peripheral leukocytes (Schmidt et al., 1977). 

Skin fibroblast or bone marrow transplantation has been used in treating Hurler s and Sanfilippo s syndromes (Dean et al., 1979 Hobbs et al., 1981 Benson, 1982 Navari et al., 1984) as an alternative to enzyme infusion therapy. At 13 months after grafting, the enzymic activity in the leukocytes and serum of the recipients reached heterozygote levels and some patients showed a remarkable clinical improvement (Rappeport and Ginns, 1984 Barranger, 1984). Only a few patients have responded to this treatment, and in others there was no evidence of clinical improvement (Munnich et al., 1982 Dean et al., 1982). Thus more trials of skin fibroblast and bone marrow transplantation are required for judging the usefulness of these procedures. 

D13. Dean, M. F, Benson, P. F., and Muir, H., The effect of itrfusions of normal plasma in three patients with Sanfilippo s syndrome. Biochem, Soc, Trans. 1, 284-287 (1973). 

Sanfllippo s syndrome (type III) This syndrome exhibits a similar clinical picture as described above with at least two different enzyme defects heparan-sulphamidase deficiency (type A) and N-acetyl-a-D-glucosamidase deficiency (type B) and possibly types C or D as well (S. X Sanfilippo et at, 1963). 

Sanfilippo, S. j., j. Yunis, and H. G. Worthen An unusual storage disease resembling the Hunter-Hurler-Syndrome. Amer. J. Dis. Child. 104, 553 (1962). 

The reduction (to roughly one-sixth) in the molecular weight of the intracellular heparan sulphate in the fibroblasts of patients with Sanfilippo B or Scheie s syndromes has been attributed to the actions of an ewdb-glycosaminidase and an e c/o-hexuronidase. Immunochemical evidence has been obtained for the presence of a defective 2-acetamido-2-deoxy-a-D-glucosidase in the tissues of patients with Sanfilippo B disease, and that, in addition to arylsulphatase B, other enzymes are present in the corrective factor for Maroteaux-Lamy disease. Arylsulphatases A and B have been separated by chromatography on DEAE-cellulose. ... 

Kimura, A., Hayashi, S., Koseki, M., Kochi, H., and Tsurumi, K., Fractionation and characterization of urinary heparan sulfate excreted by patients with Sanfilippo syndrome. Tohoku J. Exp. Med. 144, 23.7-236 (1984). 

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