Disease relevance of Mucopolysaccharidosis II

• Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-chromosomal storage disorder due to deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS) [1].
• Severe aortic stenosis in systemic lupus erythematosus and mucopolysaccharidosis type II (Hunter's syndrome) [2].
• Mutations of the IDS gene result in an X-linked lysosomal storage disease, Hunter syndrome [3].

High impact information on Mucopolysaccharidosis II

• The Hunter syndrome gene, which causes iduronate sulfatase deficiency, is located at the X chromosome breakpoint that is distal to this new marker, thus localizing the Hunter gene distal to the fragile X locus [4].
• It encompasses the fragile X (FRAXA) and Hunter syndrome (IDS) loci, and the DXS304 and DXS455 markers, in Xq27.3 and proximal Xq28 [5].
• We have developed a procedure for testing iduronate sulfatase, the enzyme deficient in Hunter syndrome, in single hair roots [6].
• X-linked Hunter syndrome: the heterozygous phenotype in cell culture [7].
• Mucopolysaccharidosis type II (MPSII; Hunter syndrome) is a lysosomal storage disorder caused by a deficiency in the enzyme iduronate 2-sulfatase (IDS) [8].

Chemical compound and disease context of Mucopolysaccharidosis II

• Chromatograms of the chondroitin ABC lyase digests of samples from nine patients with Hunter's syndrome all showed a major peak for unsaturated disaccharide-4-sulfate, derived from dermatan sulfate, and another specific but unidentified peak (peak x) [9].
• Reliability of the use of fructose 1-phosphate to detect Hunter cells in fibroblast-cultures of obligate carriers of the Hunter syndrome [10].
• After BMT, the pMPS/creatine ratio in white matter lesions of patient 3, with Hunter syndrome, was slightly decreased, but in none of the patients was the ratio ever below the control ratios, even 7 y after BMT [11].
• Specific odds of a female being a carrier of Hunter syndrome were based on serum levels of iduronate 2-sulphate sulphatase activity [12].
• We present a case of an 8-mo-old infant with Hunter's syndrome who was maintained on very large doses of fentanyl and midazolam and who could not be weaned from these drugs by conventional taper [13].

Biological context of Mucopolysaccharidosis II

• Iduronate sulfatase analysis of hair roots for identification of Hunter syndrome heterozygotes [14].
• A recently isolated cDNA clone from the iduronate sulfatase (IDS) gene has been used both to seed a contig of overlapping yeast artificial chromosomes (YACs) and to investigate the molecular defect in patients with Hunter syndrome (MPS II) [15].
• Eight unrelated patients with Hunter syndrome were investigated for expression of iduronate-2-sulfatase (IDS) mRNA by reverse transcription (RT) linked to polymerase chain reaction (PCR), or RT-PCR [16].
• We have identified the mutations in the iduronate-2-sulfatase (IDS) gene of five unrelated Norwegians with Hunter syndrome by reverse transcription-polymerase chain reaction (RT-PCR) analysis of IDS mRNA followed by single strand conformation polymorphism (SSCP) analysis and cDNA sequencing [17].
• The maximum lod score for the linkage between factor IX and the Hunter Syndrome locus was 0.424 at theta = 0.25; and that for the linkage between the Hunter Syndrome locus and DX13 was 3.01 at theta = 0.1 [18].

Anatomical context of Mucopolysaccharidosis II

• Genetic complementation in heterokaryons of MSD fibroblasts and cells of either Sanfilippo A or Hunter syndrome implies a genetic defect in MSD different from that causing specific sulfatase deficiencies [19].
• Owing to overexpression of IDS in that percentage of PBLMPS successfully transduced, IDS activity was increased above the deficiency found in patients with Hunter syndrome (< 20 U/mg per hr) to a level comparable with that of normal individuals (mean activity of uncultured normal leukocytes 807 U/mg per hr; SD 252) [20].
• Iduronate sulfatase activity in serum, lymphocytes, and fibroblasts--simplified diagnosis of the Hunter syndrome [21].
• Iduronate sulfatase in amniotic fluid: an aid in the prenatal diagnosis of the hunter syndrome [22].
• Iduronate-2-sulfatase (IDS) is involved in the degradation of heparan sulfate and dermatan sulfate in the lysosomes, and a deficiency in this enzyme results in Hunter syndrome [23].

Gene context of Mucopolysaccharidosis II

• Mucopolysaccharidosis type I (i.e., Hurler, Hurler-Scheie, and Scheie syndromes) and type II (i.e., Hunter syndrome) are lysosomal storage disorders resulting from alpha-L-iduronidase (IDUA) deficiency and iduronate-2-sulfatase (IDS) deficiency, respectively [24].
• Deletions of the IDS gene can include a conserved locus that is tightly linked to FRAXA, suggesting that deletion of nearby genes may contribute to the variable clinical severity noted in Hunter syndrome [25].
• Mutations causing IDS deficiency in humans result in the lysosomal storage of these glycosaminoglycans and Hunter syndrome, an X chromosome-linked disease [26].
• Despite the successful use of hematopoietic cell transplantation for a variety of lysosomal and peroxisomal storage diseases, limited benefit occurs following transplantation in either the severe or mild forms of Hunter syndrome [27].
• Expression of iduronate-2-sulfatase (IDS) from three different promoters in four retroviral vectors was studied in peripheral blood lymphocytes from patients with Hunter syndrome (PBL(MPS)), i.e., the LTR in vectors L2SN and L2, avian beta-actin promoter in LB2, and the CMV early promoter in LNC2 [28].

References