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Clinical and Genetic Characteristics of Romanian Patients with Mucopolysaccharidosis Type II.

ABSTRACT: BACKGROUND:Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare X-linked disorder caused by deficiency of iduronate-2-sulfatase (I2S) enzyme, which leads to the accumulation of partially digested glycosaminoglycans (GAGs) in the lysosomes and induces multisystemic alteration (coarse facial features; skeletal dysplasia; hepatosplenomegaly; joint stiffness and contractures; heart, lung, vision, and hearing disability; profound neurological decline).The purpose of this study is to present the clinical and genetic characteristics of Romanian patients with Hunter syndrome and the genotype-phenotype correlation. MATERIAL AND METHODS:15 unrelated patients, with MPS II ranging from mild (4 subjects) to severe phenotype (11 subjects) aged 2 to 20 years, were evaluated clinically, cognitive development, enzyme assay and molecular analysis. RESULTS:The molecular analysis of the 15 unrelated Romanian MPS II patients has identified 15 different mutations (2 major genetic defects (13%) and 13 minor genetic defects (87%)): microdeletions and point mutations (missense, nonsense), seven of them described for the first time-deletion encompassing 3 to exon 7; c823G>T, pD275Y; c.1600A>C (pN534H); c.102_10delAG (p.D5Cfs*11); c.448_471del (p.P150_P157del); c.421delA (p.I141Yfs*72); and c.419-1G>C. The major genetic defects were correlated with a severe course of disease. CONCLUSION:This is the first study on the clinical and molecular characterization of the MPS II Romanian patients. This study supports the evidence of the mutational heterogeneity of the I2S gene as well as the difficulty to correlate genotype and phenotype in the patients with MPS II.

SUBMITTER: Alkhzouz C

PROVIDER: S-EPMC5413445 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Clinical and Genetic Characteristics of Romanian Patients with Mucopolysaccharidosis Type II.

Alkhzouz Camelia C Lazea Cecilia C Bucerzan Simona S Nascu Ioana I Kiss Eva E Denes Carmencita Lucia CL Grigorescu-Sido Paula P

JIMD reports 20160629

<h4>Background</h4>Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare X-linked disorder caused by deficiency of iduronate-2-sulfatase (I2S) enzyme, which leads to the accumulation of partially digested glycosaminoglycans (GAGs) in the lysosomes and induces multisystemic alteration (coarse facial features; skeletal dysplasia; hepatosplenomegaly; joint stiffness and contractures; heart, lung, vision, and hearing disability; profound neurological decline).The purpose of this study is ...[more]

PMID: 27351199

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Project description:Background: Mucopolysaccharidosis II (MPS II; Hunter syndrome) is a rare, X-linked, life-limiting lysosomal storage disease characterized by a deficiency in the activity of the enzyme iduronate-2-sulfatase. Accumulation of glycosaminoglycans in tissues and organs throughout the body causes cellular damage, leading to multisystemic disease manifestations. Patients generally require multidisciplinary care across a wide range of specialties. Objectives: The aims of this study were to assess the healthcare needs of patients with MPS II and to explore the impact of treatment on disease burden and healthcare resource utilization. Methods: A retrospective review of medical charts from 19 US sites was performed. Data were analyzed from 140 male patients diagnosed with MPS II (defined as a documented deficiency in iduronate-2-sulfatase) between 1997 and 2017. The prevalence and age at onset of clinical manifestations and extent and frequency of healthcare resource use were evaluated. Results: Of the patients in this study, 77.1% had received enzyme replacement therapy with intravenous idursulfase and 62.1% had cognitive impairment. The clinical burden among patients was substantial: almost all patients had ear, nose, and throat abnormalities (95.7%); musculoskeletal abnormalities (95.0%); and joint stiffness or abnormalities (90.7%). Of the most prevalent disease manifestations, facial dysmorphism and hepatosplenomegaly were documented the earliest (median age at first documentation of 3.8 years in both cases). Hospitalizations, emergency department visits, and outpatient visits were reported for 51.2%, 58.5%, and 93.5% of patients, respectively, with a frequency of 0.1, 0.2, and 3.0 per patient per year, respectively. Surgery was also common, with 91.1% of patients having undergone at least 1 surgical procedure. The clinical burden and prevalence and frequency of resource use were generally similar in patients who had received enzyme replacement therapy and in those who had not. Conclusions: These results add to our understanding of the natural history of MPS II and indicate that the disease burden and healthcare needs of patients with this progressive disease are extensive. Increased understanding of disease burden and resource use may enable the development of models of healthcare resource utilization in patients with MPS II and contribute to improvements in disease management and patient care.

Project description:Background and objective Mucopolysaccharidosis type II (MPS II; Hunter syndrome; OMIM +309900) is an X-linked recessive, multisystemic lysosomal storage disorder caused by iduronate-2-sulfatase (I2S) deficiency, which catalyzes a step in the catabolism of glycosaminoglycans (GAGs). It leads to accumulation of GAGs in the lysosomes of many organs and tissues, causing progressive cellular dysfunction. MPS II has a variable age of onset and variable rate of progression. In Asian countries, there is a relatively higher incidence of MPS II compared to other types of MPS. The study aims to delineate the cause of death and natural history of Taiwanese patients with MPS II. Methods A retrospective analysis was carried out of 34 Taiwanese MPS II patients who died between 1995 and 2012. The clinical characteristics, medical records, age at death, and cause of death were evaluated to better understand the natural progression of this disease. Results Among these 34 mortality patients, 31 were severe form with significant cognitive impairment, two were mild form without cognitive involvement, and one was intermediate form. The mean age at death was 14.2±4.2 years. The mean ages at onset of symptoms and confirmed diagnosis were 2.5±2.1 and 4.8±3.1 years, respectively (n=32). The mean gestational age and birth weight were 39.2±1.8 weeks and 3,522±581 grams, respectively (n=24). The mean age at death of 31 severe form was 13.2±3.2 years, compared with 22.6±4.3 years of three patients with mild or intermediate forms (P<0.001). Among the 27 patients with available records of primary cause of death, respiratory failure was the leading cause (70%), followed by cardiac failure (22%), post-traumatic organ failure (4%), and infection (sepsis) (4%). Age at onset of symptoms was positively correlated with life expectancy (P<0.01). The longevity also increased gradually over time between 1995 and 2012 (P<0.05). Conclusions The life expectancy of Taiwanese MPS II patients has improved in recent decades. With the implementation of National Health Insurance in Taiwan since 1995, it is possible that referral of patients to specialist and improvement in multidisciplinary care underlie this trend. These findings can be used to develop quality of care strategies for these patients.

Dataset Information

Clinical and Genetic Characteristics of Romanian Patients with Mucopolysaccharidosis Type II.

Publications

Clinical and Genetic Characteristics of Romanian Patients with Mucopolysaccharidosis Type II.

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