Mucopolysaccharidosis Type II and the G374sp Mutation

Martínez‐Quintana, Efrén; Rodríguez‐González, Fayna

doi:10.1159/000346842

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…Patient with this variant showed an attenuated phenotype. Molecular analysis of MPS II patients identified a recurrent splice site variant p.Gly374sp reported to be involved in the disruption of cryptic splice site resulting in the deletion of 20 amino acids downstream of IDS protein due to the loss of constitutive splice site (27). The pathogenic variant p.Gly374sp in Indian population was found to be always associated with both severe and attenuated phenotypes.…”

Section: Hurler Syndromementioning

confidence: 99%

Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II

et al. 2016

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Mucopolysaccharidoses (MPS), a subgroup of lysosomal storage disorders, are caused due to deficiency of specific lysosomal enzyme involved in catabolism of glycosaminoglycans. To date more than 200 pathogenic variants in the alpha-l-iduronidase (IDUA) for MPS I and ∼500 pathogenic variants in the iduronate-2-sulphatase (IDS) for MPS II have been reported worldwide. The mutation spectrum of MPS type I and MPS type II disorders in Indian population is not characterized yet. In this study, we carried out clinical, biochemical, molecular and in silico analyses to establish the mutation spectrum of MPS I and MPS II in the Indian population. We conducted molecular analysis for 60 MPS-affected patients [MPS I (n = 30) (Hurler syndrome = 17, Hurler-Scheie syndrome = 13), and MPS II (n = 30) (severe = 18, attenuated = 12)] and identified a total of 44 [MPS I (n = 22) and MPS II (n = 22)] different pathogenic variants comprising missense, nonsense, frameshift, gross deletions and splice site variants. A total of 20 [MPS I (n = 14), and MPS II (n = 6)] novel pathogenic sequence variants were identified in our patient cohort. We found that 32% of pathogenic variants detected in IDUA were recurrent and 25% in MPS II. This is the first study revealing the mutation spectrum of MPS I and MPS II patients in the Indian population.

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Section: Hurler Syndromementioning

confidence: 99%

Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II

et al. 2016

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“…To date, more than 370 different mutations of the I2S gene and they are related to different clinical disorders. Due to this heterogeneity the choice of therapeutic management is an arduous challenge for paediatricians [3].…”

Section: Discussionmentioning

confidence: 99%

“…MPS II, also known as Hunter syndrome, is an X-linked disease with deficiency of enzyme iduronate 2-sulfatase (I2S). This results in an accumulation of dermatan sulfate and heparin sulfate in many organs (skin, blood vessels, heart and heart valves, lung, airways, central nervous system) [1][2][3]. Historically, the treatment of MPS II has been palliative.…”

Section: Introductionmentioning

confidence: 99%

Hunter Syndrome: First Italian Case Treated With Enzyme-Replacement Therapy. Ten Years of Follow-Up

et al. 2017

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The Hunter syndrome (Mucopolysaccharidosis II, MPS II) is a severe genetic disease (X-linked recessive). Its incidence is about 0.3-0.71 per 100 000 live births. It is caused by the deficiency in the lysosomal enzyme iduronate-2-sulphatase (I2S), which catalyses the degradation of the glycosaminoglycans (GAG). This leads to a widespread accumulation of the GAG dermatan and heparan sulphate in many organs with a final progressive multi-system disease. The enzyme-replacement therapy (ERT) with idursulfase, a recombinant human I2S enzyme, is now available (since 2006) in many countries. We described the first case treated in Italy with this method. A 13-month-old male arrived to our Clinic and was diagnosed with MPS II. He was treated with ELAPRASE (0.5 mg/kg intravenously administered every week) since 32 months of age. We monitored the urinary GAG content, the patient’s detailed anthropometric (growth, weight, phenotypic aspects of the face, as well as chest, limbs and whole body), joint range of motion and skeletal radiographs, ultrasound studies of liver and spleen volumes, the distance covered in the 6-minute walk test and respiratory symptoms, echocardiography and heart valvulopathies, otorinolaryngological symptoms, audiological examinations, pain, neurological involvement and psychological tests. The patient was treated for 10 years and he is still in treatment. He now presents i) significant reduction in GAG levels in the biological fluids, ii) important improvements in lung function, in the ability of walking, in other visceral organs function and iii) a significant reduction of the liver and spleen volumes. We can conclude that an early diagnosis is fundamental for an efficient therapy of the Hunter syndrome disease. Indeed the treatment of patients with MPS II before the onset of clinical symptoms may significantly improve the quality of life and the survival. The ELAPRASE treatment is a good option for these patients, but not all patients with MPS II may be elected for this type of treatment. An accurate selection is fundamental also based on high cost of medication.

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“…The syndrome occurs in all ethnic groups, but a higher incidence has been reported among the Jews in Israel (3). The incidence ranges from one case per 72,000 male live births in Northern Ireland to one case per 518,000 male live births in British Columbia (4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Challenges in the Management of Mucopolysaccharidosis Type II (Hunter’s Syndrome) in a Developing Country: a Case Report

Rasheeedah¹,

Patrick²,

Abdullateef³

et al. 2015

Ethiop J Health Sci

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BACKGROUND: Mucopolysaccharidosis type II (Hunter's syndrome) is an X-linked chromosomal storage disorder due to deficiency of the lysosomal enzyme iduronate-2-sulfatase with patients rarely living till adulthood. Failure to identify patients early could contribute to an increased morbidity as identified in this case report. CASE DETAILS: An eight year old patient with Hunter's syndrome identified five years after disease onset with severe cardiovascular complications exemplifies the challenges faced in resource-limited countries towards making diagnosis and treatment of rare conditions. Elevated urinary glycosaminoglycans levels or a strong clinical suspicion of Hunter's syndrome, as identified in the index case, is a prerequisite for enzyme activity testing. Urinary mucopolysaccharide(MPS) level was 69.6mg/mmol(normal range is 0.0 -11.6mg/mmol), and the confirming MPS electrophoresis analysis showed elevated heparan sulphate in the urine sample. Enzyme activity testing, with absent or very low iduronate-2-sulfatase activity, is diagnostic. However, the scarce availability and high cost of these tests is another constraint in making a diagnosis. CONCLUSION: Identification and management of mucopolysaccharidosis type II pose a problem in resource-constrained countries due to late presentation, lack of facility for diagnosis and treatment, cost and expertise required for the management.

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Mucopolysaccharidosis Type II and the G374sp Mutation

Cited by 5 publications

References 20 publications

Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II

Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II

Hunter Syndrome: First Italian Case Treated With Enzyme-Replacement Therapy. Ten Years of Follow-Up

Challenges in the Management of Mucopolysaccharidosis Type II (Hunter’s Syndrome) in a Developing Country: a Case Report

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