A clinical and genetic study of Hunter's syndrome. 2 Differences between the mild and severe forms

Young, Ian; Harper, P S; Newcombe, Robert G.; Archer, Irene M.

doi:10.1136/jmg.19.6.408

Cited by 112 publications

(85 citation statements)

References 8 publications

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“…Reasons for the discrepancy would be partly due to the manner of classifying the severity of Hunter disease. The conventional classification has been defined mainly according to the severity regarding intelligence (Young et al 1982). However, some patients with severe mental disability have relatively mild somatic manifestations, and vice versa (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Mutational and structural analysis of Japanese patients with mucopolysaccharidosis type II

Kato

Kuratsubo

et al. 2005

J Hum Genet

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We investigated mutations of the iduronate-2-sulfatase (I2S) gene and structural characteristics of I2S to clarify genotype/phenotype relationships in 18 Japanese patients with mucopolysaccharidosis type II. The I2S gene was analyzed in five patients with a severe phenotype and in 13 patients with an attenuated phenotype. The tertiary structural model of the human I2S was constructed by homology modeling using the arylsulfatase structure as a template. We identified four missense mutations and a nonsense mutation in the severe phenotype; four missense, two nonsense, three frame shifts, and one each of splice and amino acid deletion in the attenuated phenotype. Seven of them (L73del, Q75X, G140R, C171R, V401 fs, C422 fs, and H441 fs) were novel mutations. Structural analysis indicated that the residues of the mutations found in the severe phenotype would have direct interactions with the active site residues or should break the hydrophobic core domain of I2S, whereas residues of the missense mutations found in the attenuated phenotype were located in the peripheral region. In addition, effects by deletion or frameshift mutations could also be interpreted by the structure. Structural analysis of mutant proteins would help in understanding the genotype/phenotype relationships of Hunter disease.

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Section: Discussionmentioning

confidence: 99%

Mutational and structural analysis of Japanese patients with mucopolysaccharidosis type II

Kato

Kuratsubo

et al. 2005

J Hum Genet

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“…About two-thirds of patients have cognitive impairment and/or behavioral abnormalities (Froissart et al 1998, Vafiadaki et al 1998. These patients are often described as having the severe phenotype, and they typically only survive into the second and occasionally the third decade of life (Jones et al 2009, Young andHarper 1983;Young et al 1982b). Patients with the attenuated phenotype do not have cognitive impairment; however, they can experience all of the somatic signs and symptoms of the disease, although often with a more gradual onset.…”

Section: Introductionmentioning

confidence: 99%

Enzyme Replacement Therapy in Mucopolysaccharidosis II Patients Under 1 Year of Age

et al. 2014

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Mucopolysaccharidosis (MPS) II, or Hunter syndrome, is a lysosomal storage disease characterized by multi-systemic involvement and a progressive clinical course. Enzyme replacement therapy with idursulfase has been approved in more than 50 countries worldwide; however, safety and efficacy data from clinical studies are currently only available for patients 1.4 years of age and older. Sibling case studies of infants with MPS I, II, and VI who initiated ERT in the first weeks or months of life have reported no new safety concerns and a more favorable clinical course for the sibling treated in infancy than for the later-treated sibling. Here we describe our experiences with a case series of eight MPS II patients for whom idursulfase treatment was initiated at under 1 year of age. The majority of the patients were diagnosed because of a family history of disease. All of the infants displayed abnormalities consistent with MPS II at diagnosis. The youngest age at treatment start was 10 days and the oldest was 6.5 months, with duration of treatment varying between 6 weeks and 5.5 years. No new safety concerns were observed, and none of the patients experienced an infusion-related reaction. All of the patients treated for more than 6 weeks showed

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“…In patients with cognitive impairment, somatic involvement is usually severe and of early onset and may include coarse facial features, bone and joint abnormalities, short stature, respiratory and cardiac disease and hearing abnormalities. Somatic involvement in patients without cognitive impairment can range from being severe with early onset to much less severe with later onset (Young et al 1982;Young and Harper 1983;Neufeld and Muenzer 2001;Schwartz et al 2007;Wraith et al 2008b); this group of patients usually exhibits minimal or no neurological involvement. Management of patients with MPS II requires a multidisciplinary approach involving a range of specialties such as cardiology, neurology, psychology, pulmonology and orthopaedics (Wraith et al 2008a;Muenzer et al 2009;Scarpa et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Survival in idursulfase‐treated and untreated patients with mucopolysaccharidosis type II: data from the Hunter Outcome Survey (HOS)

Burton

Jego²,

Mikl

et al. 2017

J of Inher Metab Disea

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Mucopolysaccharidosis type II (MPS II; Hunter syndrome; OMIM 309900) is a life-limiting, multisystemic disease with varying presentation and severity. Enzyme replacement therapy with intravenous idursulfase (EC 3.1.6.13) has been available since 2006. Data from the Hunter Outcome Survey (July 2016) were used to compare survival in idursulfase-treated (n = 800) and untreated (n = 95) male patients followed prospectively in this multinational, observational registry. Median age at symptom onset was similar for the treated and untreated groups (1.6 and 1.5 years, respectively), as was median age at diagnosis (3.3 and 3.2 years) and the proportion of patients with cognitive impairment (58.0%; 57.9%). 33.0 (30.4, 38.4) years in treated patients and 21.2 (16.1, 31.5) years in untreated patients; median follow-up time from birth to death or last visit was 13.0 and 15.1 years, respectively. A Cox model adjusted for treatment status, cognitive impairment, region and age at diagnosis indicated a 54% lower risk of death in treated compared with untreated patients: hazard ratio (HR), 0.46 (95% CI: 0.29, 0.72). Patients with cognitive impairment had nearly a fivefold higher risk of death than those without (HR, 4.84 [3.13, 7.47]). This analysis in a large population of patients with MPS II indicates for the first time that idursulfase treatment is associated with increased survival.

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A clinical and genetic study of Hunter's syndrome. 2 Differences between the mild and severe forms

Cited by 112 publications

References 8 publications

Mutational and structural analysis of Japanese patients with mucopolysaccharidosis type II

Mutational and structural analysis of Japanese patients with mucopolysaccharidosis type II

Enzyme Replacement Therapy in Mucopolysaccharidosis II Patients Under 1 Year of Age

Survival in idursulfase‐treated and untreated patients with mucopolysaccharidosis type II: data from the Hunter Outcome Survey (HOS)

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