Iduronate-2-sulfatase

Idursulfase (Elaprase) is a drug used to treat mucopolysaccharidosis II or Hunter syndrome. It is a lysosomal storage disease caused by iduronate-2-sulfatase deficiency. Idursulfase is a purified form of iduronate-2-sulfatase produced by recombinant DNA technology in a human cell line. The drug provides clinically important benefits to Hunter syndrome patients. After intravenous infusion Idursulfase is eliminated by peptide hydrolysis with an elimination half-life of 45 minutes. The most common adverse events are hypersensitivity reactions, pyrexia, headache and arthralgia. 

J 11 Hunter (mild or severe) 309900 Dermatan sulfate Heparan sulfate Iduronate-2-sulfatase Xq28... 

Cell-free amniotic fluid and cultured amniocytes Iduronate 2-sulfatase... 

Hurler-Scheie (MIM 252800) Hunter (MIM 309900) MPS II Iduronate sulfatase Dermatan sulfate, heparan sulfate... 

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

Hunter syndrome (MPS-II) is an X-linked disorder arising from deficiency of iduronate sulfatase,... 

MPS II (Hunter) Iduronate sulfatase Dermatan sulfate, heparan sulfate Skeletal, bone, organomegaly, neurological Mouse, dog Plasmid IM (Tomanin et al., 2002)... 

The mucopolysaccharidoses are classified into seven clinical types and all are transmitted by autosomal recessive inheritance except for Hunter syndrome (MPS II, iduronate sulfatase deficiency), which is an X-linked disorder. Diagnosis of the specific disorder is made by measuring the specific enzyme activities in leukocytes or cultured skin fibroblasts. Because it takes some time... 

B. All of the mucopolysaccharidoses are transmitted by autosomal recessive inheritance except Hunter syndrome (MPS II), a deficiency in iduronate sulfatase that is X-linked recessive. Since Hunter syndrome is X-linked, it is almost exclusively seen in males. Since our patient is female, she would not be expected to have an X-linked disorder. 

E. Since this patient is suspected of having Hunter syndrome, a deficiency in iduronate sulfatase, iduronate 2-sulfate would be expected to be present at the nonreducing end of glycosaminoglycans found in this patient s urine. A deficiency of iduronate sulfatase would prevent the sulfate ester bond of iduronate 2-sulfate residues from being hydrolyzed and further degradation of the glycosaminoglycan would be halted. 

Liebaers, I., and Neufeld, E. F., Iduronate sulfatase activity in serum, lymphocytes and fibroblasts—simplified diagnosis of the Hunter syndrome. Pediatr. Res. 10, 733-736 (1976). 

Yutaka, T., Fluharty, A. L., Stevens, R. L., and Kihara, H., Iduronate sulfatase analysis of hair roots for identification of Hunter syndrome heterozygotes. Am, J. Hum. Genet. 30, 575-582... 

This enzyme [EC 3.1.6.18], also known as glucuronate-2-sulfatase and chondro-2-sulfatase, catalyzes the hydrolysis of the 2-sulfate groups of the 2-O-sulfo-D-glucuro-nate residues of chondroitin sulfate, heparin, and hepari-tin sulfate. The enzyme does not act on iduronate 2-sulfate residues. 

This enzyme [EC 3.1.6.13], also known as iduronate-2-sulfate sulfatase and chondroitinsulfatase, catalyzes the... 

Sulfotransferases917 920a transfer sulfo groups to O and N atoms of suitable acceptors (reaction type ID, Table 10-1). Usually, transfer is from the "active sulfate," 3 -phosphoadenosine 5 -phosphosuIfate (PAPS),921 whose formation is depicted in Eq. 17-38. Sulfatases catalyze hydrolysis of sulfate esters. The importance of such enzymes is demonstrated by the genetic mucopolysaccharidoses. In four of these disease-specific sulfatases that act on iduronate sulfate, heparan N-sulfate, galactose-6-sulfate, or N-acetylglu-cosamine-4-sulfate are absent. Some of these, such as heparan N-sulfatase deficiency, lead to severe mental retardation, some cause serious skeletal abnormalities, while others are mild in their effects.922... 

The missing enzyme is a sulfatase for 2-sulfated iduronate residues.354 355 The diagram at the bottom of the page illustrates the need for both of these enzymes as well as three others in the degradation of dermatan 352/356/357... 

Timms KM, Lu F, Shen Y, Pierson CA, Muzny DM, Gu Y, Nelson DL, Gibbs RA. 130 kb of DNA sequence reveals two new genes and a regional duplication distal to the human iduronate-2-sulfate sulfatase locus. Genome Res 1995 5(l) 71-78. 

MPII, Hunter Iduronic acid-O-2 sulfate sulfatase HS, DS... 

Eliahu, R., Sekeles, E., Cohen, R., and Bach, G., The correction of Hunter fibroblasts by enogenous iduronate sulfate sulfatase Biochemical and ultrastructural studies. Am. J. Hum. Genet. 33, 576-583 (1981). 

Hunter Hurler + Scheie Maroteaux-Lamy Mucolipidosis Vli Sanfilippo A Sanfilippo B Sanfilippo D iduronate suifatase a-L-iduronidase A/-Acetylgalactosamine suifatase p-Glucuronidase Heparan sulfamidase A/-Acetylglucosaminidase A/-Acetylglucosamine 6-sulfatase Heparan sulfate. Dermatan sulfate Heparan sulfate. Dermatan sulfate Dermatan sulfate Heparan sulfate. Dermatan sulfate Heparan sulfate Heparan sulfate Heparin sulfate... 

---