Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hunter syndrome is a human X-linked disorder caused by deficiency of the lysosomal exohydrolase iduronate-2-sulphatase (IDS). The consequent accumulation of the mucopolysaccharides dermatan sulphate and heparan sulphate, in the brain and other tissues, often results in death before adulthood. There is, however, a broad spectrum of severity that has been attributed to different mutations of the Hunter syndrome gene. We have used an IDS cDNA clone to localise the IDS gene to Xq28, distal to the fragile X mutation (FRAXA). One-third of Hunter syndrome patients had various deletions or rearrangements of their IDS gene, proving that different mutations are common in this condition. 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. The cDNA clone was also shown to span the X chromosome breakpoint in a female Hunter syndrome patient with an X;autosome translocation.
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PMID:Frequent deletions at Xq28 indicate genetic heterogeneity in Hunter syndrome. 190 26

Severe Hunter syndrome is a fatal X-linked lysosomal storage disorder caused by iduronate-2-sulphatase (IDS) deficiency. Patients with complete deletion of the IDS locus often have atypical phenotypes including ptosis, obstructive sleep apnoea, and the occurrence of seizures. We have used genomic DNA sequencing to identify several new genes in the IDS region. DNA deletion patients with atypical symptoms have been analysed to determine whether these atypical symptoms could be due to involvement of these other loci. The occurrence of seizures in two individuals correlated with a deletion extending proximal of IDS, up to and including part of the FMR2 locus. Other (non-seizure) symptoms were associated with distal deletions. In addition, a group of patients with no variant symptoms, and a characteristic rearrangement involving a recombination between the IDS gene and an adjacent IDS pseudogene (IDS psi), showed normal expression of loci distal to IDS. Together, these results identify FMR2 as a candidate gene for seizures, when mutated along with IDS.
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PMID:Molecular and phenotypic variation in patients with severe Hunter syndrome. 914 53

Hunter syndrome is a rare, X-linked, recessively inherited disease affecting approximately 1 in 132,000 males. The disease is caused by the inability to degrade dermatan sulphate and heparan sulphate due to mutations in the iduronate-2-sulphatase gene (IDS). The mutations causing the disorder are heterogeneous, ranging from small micro-lesions to gross deletions and inversions. We have screened DNA samples from a panel of 24 unrelated Hunter syndrome patients and have identified mutations in 16 individuals. Six mutations represent novel changes in the gene and these include two single base deletions (1264DC and 1632/3DT); two single base insertions (776/8insC and 1082insT); and two missense mutations--Y264N (914T-->G) and Q465P (1518A-->C). An additional two missense mutations and one splice site alteration identified in this study have been described previously. Southern analysis revealed complete or partial gene deletions in a further 7 patients.
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PMID:Mutation analysis of iduronate-2-sulphatase gene in 24 patients with Hunter syndrome: characterisation of 6 novel mutations. Mutation in brief no. 249. Online. 1044 64

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked disease caused by a deficiency of the enzyme iduronate-2-sulphatase (IDS), which results in the lysosomal accumulation of glycosaminoglycans (GAG). This paper describes a knockout mouse model of MPS II which has been used to assess the effect of enzyme replacement therapy. Therapy with IDS results in a marked decrease in urinary GAGs, as well as reduced GAG accumulation in several tissues. These studies have been used to support the first clinical trial of recombinant IDS in patients with Hunter syndrome.
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PMID:Enzyme replacement therapy in mucopolysaccharidosis type II (Hunter syndrome): a preliminary report. 1257 50

The mucopolysaccharidoses (MPS) are characterized by the accumulation of glycosaminoglycans (GAG) and result from the impaired function of one of 11 enzymes required for normal GAG degradation. MPS II was the first MPS to be defined clinically in humans and is caused by deficient activity of the enzyme iduronate-2-sulphatase. MPS VI was the first MPS recognized in an animal; since then, all but MPS IIIC and IX have been described as naturally occurring in animals or made by knock-out technology. As in humans, all are inherited as autosomal recessive traits, except for MPS II, which is X-linked. Most animal colonies have been established from single related heterozygous animals, making the affected offspring homozygous for the same mutant allele. Importantly, these models have disease pathology that is similar to that seen in humans, making the animals extremely valuable for the investigation of disease pathogenesis and the testing of therapies. Large animal homologues are similar to humans in natural genetic diversity, approaches to therapy and care, and the possibility of evaluating long-term effects of treatment. Therapeutic strategies for MPS include enzyme replacement therapy, heterologous bone marrow transplantation, and somatic cell gene transfer, all of which have been tested in animals with some success.
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PMID:Animal models for mucopolysaccharidoses and their clinical relevance. 1257 49

Hunter syndrome (mucopolysaccharidosis type II [MPS II], OMIM309900) is a rare X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulphatase, resulting in accumulation of glycosaminoglycans (GAGs), multisystem organ failure and early death. Enzyme replacement therapy (ERT) with idursulfase is commercially available since 2007. Early access programs were established since 2005. However, limited information on the effects of ERT in young children is available to date. The aim of this analysis was therefore to determine the effects of ERT on patients younger than 5 years of age. We report data from six Spanish patients with confirmed Hunter syndrome who were younger than 5 years at the start of ERT, and had been treated with weekly intravenous infusions of idursulfase between 6 and 14 months. Baseline and treatment data were obtained from the Hunter Outcome Survey (HOS). HOS is an international database of MPS II patients on ERT or candidates to be treated, that collects data in a registry manner. HOS is supported by Shire Human Genetic Therapies, Inc. (Cambridge, MA, USA). At baseline, all patients showed neurological abnormalities, including ventriculomegaly, hydrocephaly, cerebral atrophy, perivascular changes and white matter lesions. Other signs and symptoms included thoracic deformity, otitis media, joint stiffness and hepatosplenomegaly, demonstrating that children under 5 years old can also be severely affected. ERT reduced urinary GAG levels, and reduced spleen (n = 2) and liver size (n = 1) after only 8 months. Height growth was maintained within the normal range during ERT. Joint mobility either stabilized or improved during ERT. In conclusion, this case series confirms the early onset of signs and symptoms of Hunter syndrome and provides the first evidence of ERT beneficial effects in patients less than 5 years of age. Similar efficacy and safety profiles to those seen in older children can be suggested, although further studies including a direct comparison with older patients would still be required.
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PMID:First experience of enzyme replacement therapy with idursulfase in Spanish patients with Hunter syndrome under 5 years of age: case observations from the Hunter Outcome Survey (HOS). 2070 29

Mucopolysaccharidosis (MPS) type II (Hunter syndrome, OMIM 309900) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). Major clinical manifestations include joint contractures, obstructive and restrictive airway disease, cardiac disease, skeletal deformities and often mental retardation. As with all the MPS disorders, mucopolysaccharidosis type II is a clinically heterogeneous disease in terms of the extent and rate of progression of organ impairment in affected individuals. Common causes of death, which usually occurs within the second decade of life, are obstructive airway disease and cardiac failure due to valvular dysfunction, pulmonary hypertension and myocardial disease. Patients with the more attenuated (so-called adult) form usually have a normal intelligence, but often have many complaints such as progressive loss of vision due to retinal dysfunction, spastic paresis due to myelon compression at the cranio-cerevical region, severe hip disease and cardiac complications. Clinical investigations that have been performed in the last years in a great number of patients have shown that many of these complications are still underdiagnosed and untreated. Until recently, no specific treatment was available for the affected patients; management mainly consisted of supportive care and treatment of complications. Enzyme replacement therapy with recombinant iduronate-2-sulphatase (idursulfase), however, has now been introduced. And it could be demonstrated that weekly intravenous infusions of idursulfase is able to improve many of the symptoms and signs of Hunter syndrome. This review will present the efficacy and safety data of the enzyme preparation and discuss benefits and limitations of this new therapeutic option.
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PMID:Mucopolysaccharidosis Type II (Hunter Syndrome): clinical picture and treatment. 2123 46

Hunter syndrome or mucopolysaccharidosis II (MPS II) is a rare X-linked disease caused by a deficiency of the iduronate-2-sulphatase (12S) lysosomal enzyme, resulting in a progressive accumulation of glycosaminoglycans (GAGs). Enzyme replacement therapy (ERT) with recombinant human 12S idursulfase has been used infrequently in children < 5 years. We present the case of a 7 years and 10 months-old child, who was diagnosed with a severe form of MPS II at the age of 3 years, and who began a 36 months' treatment with idursulfase at 4 years 10 months. After 10 months, GAG urinary excretion was normal, but after just 4 months the liver and spleen had decreased in size, returning to normal limits by 36 months. Significant bone remodeling was noted after 16 months. Cardiac and neurological development, however, progressively deteriorated. The only adverse reactions were episodic inflammations of the upper and/or lower respiratory tract, but there was no otitis. Early use of ERT, presuming good treatment adherence, can significantly improve bone abnormalities.
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PMID:Long-term enzyme replacement therapy in a severe case of mucopolysaccharidosis type II (Hunter syndrome). 2152 70

Hunter syndrome (mucopolysaccharidosis type II [MPS II], OMIM309900) is a rare X-linked lysosomal storage disorder caused by the deficiency of the enzyme iduronate-2-sulphatase, resulting in accumulation of glycosaminoglycans, progressive multisystem organ failure, and early death. Enzyme replacement therapy (ERT) with weekly intravenous infusions of idursulfase, a treatment for MPS II and commercially available since 2007, has been shown to improve certain symptoms and signs of the disease. The efficacy and safety data of this enzyme preparation have been widely reported and, after a change to the idursulfase Summary of Product Characteristics in March 2010, home ERT by infusion is now an option for selected patients. Previously reported experiences of home therapy in MPS II have shown increased treatment compliance and an improvement in quality of life for both patients and families. We report the results of the home therapy experience of 3 paediatric patients with MPS II in southern Italy. This pilot experience with home infusion is the first reported from Italy.
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PMID:Home treatment in paediatric patients with Hunter syndrome: the first Italian experience. 2401 Dec 28

Hunter syndrome is caused by deficiency of the lysososmal enzyme iduronate-2-sulphatase that cleaves O-linked sulphate moieties from dermatan sulphate and heparan sulphate and leads to accumulation of GAGs. The disease is a X-linked condition affecting males and rarely females, clinically divided into severe (2/3) and attenuated types. Children with severe form, diagnosed at 12-36 months, have coarse facial feature, short stature, joint stiffness, short neck, broad chest, large head circumference, watery diarrhea, skeletal changes, progressive and profound mental retardation, retinal degeneration' hearing loss, cardiomyopathy, valvular involvement, with progressive thickening and stiffening of the valve leaflets leading to mitral and aortic regurgitation and stenosis . Recurrent and prolonged rhinitis with persistent nasal discharge are the first symptoms of airway disease that manifests itself as noisy breathing and later sleep apnea. Some patients develop ivory-colored skin lesions on the upper back and sides of the upper arms, pathogenomic of Hunter syndrome. The scalp hair becomes coarse, straight and bristly. Inguinal and umbilical hernias occur caused by the disturbed structure of connective tissue and increased liver and spleen volume. Patients with attenuated form have normal intelligence and a milder phenotype. Physical features diagnosed later are similar but less pronounced but progress to severe disease. Sceening is by quantitative assessment of urinary GAGs excretion. Qualitative assessment of GAG by electrophoresis can distinguish the type of mucopolysaccharidosis. Definitive diagnosis is based on enzyme activity assay in leukocytes, fibroblasts or plasma. Molecular testing is recommended mainly for genetic counseling and carrier detection. Limited experience of Haematopoietic stem cell therapy in MPS II showed progressive neurodegeneration. Recombinant 125 Idursulfase, is indicated for long-term treatment. The response appears to depend on the severity of the disease and the age treatment is started, Improvements in a composite endpoint comprising: change in walking distance percentage of predicted forced vital capacity (%FVC) ,decrease in liver and spleen volume and urinary GAG levels were encouraging. Current research is focused on pharmacological chaperones, gene therapy and substrate reduction therapy and therapies that, unlike Idursulfase, do cross the blood-brain barrier.
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PMID:Mucopolysaccharidosis type II, Hunter's syndrome. 2534 92


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