Diagnosing Lysosomal Storage Disorders: Mucopolysaccharidosis Type II

2013 ◽  
pp. 17.14.1-17.14.9 ◽  
Author(s):  
Britt A. Johnson ◽  
Otto P. van Diggelen ◽  
Angela Dajnoki ◽  
Olaf A. Bodamer
Keyword(s):  
Lysosomal Storage Disorders ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Mucopolysaccharidosis Type Ii ◽  
Storage Disorders

scholarly journals Modeling Mucopolysaccharidosis Type II in the Fruit Fly by Using the RNA Interference Approach

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 263
Author(s):  
Laura Rigon ◽  
Nicole Kucharowski ◽  
Franka Eckardt ◽  
Reinhard Bauer
Keyword(s):  
Rna Interference ◽  
Enzymatic Activity ◽  
Dermatan Sulfate ◽  
Fruit Fly ◽  
Neurological Involvement ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Mucopolysaccharidosis Type Ii ◽  
Mps Ii

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder that occurs due to the deficit of the lysosomal enzyme iduronate 2-sulfatase (IDS) that leads to the storage of the glycosaminoglycan heparan- and dermatan-sulfate in all organs and tissues. It is characterized by important clinical features and the severe form presents with a heavy neurological involvement. However, almost nothing is known about the neuropathogenesis of MPS II. To address this issue, we developed a ubiquitous, neuronal, and glial-specific knockdown model in Drosophila melanogaster by using the RNA interference (RNAi) approach. Knockdown of the Ids/CG12014 gene resulted in a significant reduction of the Ids gene expression and enzymatic activity. However, glycosaminoglycan storage, survival, molecular markers (Atg8a, Lamp1, Rab11), and locomotion behavior were not affected. Even strongly reduced, IDS-activity was enough to prevent a pathological phenotype in a MPS II RNAi fruit fly. Thus, a Drosophila MPS II model requires complete abolishment of the enzymatic activity.

scholarly journals Newborn Screening for Mucopolysaccharidosis Type II in Illinois: An Update

2020 ◽  
Vol 6 (3) ◽  
pp. 73 ◽  
Author(s):  
Barbara K. Burton ◽  
Rachel Hickey ◽  
Lauren Hitchins
Keyword(s):  
Newborn Screening ◽  
Early Years ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Mucopolysaccharidosis Type Ii ◽  
Effective Treatment Option ◽  
Positive Screen ◽  
Enzyme Replacement ◽  
Mps Ii

Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare, progressive multisystemic lysosomal storage disorder with significant morbidity and premature mortality. Infants with MPS II develop signs and symptoms of the disorder in the early years of life, yet diagnostic delays are very common. Enzyme replacement therapy is an effective treatment option. It has been shown to prolong survival and improve or stabilize many somatic manifestations of the disorder. Our initial experience with newborn screening in 162,000 infants was previously reported. Here, we update that experience with the findings in 339,269 infants. Measurement of iduronate-2-sulfatase (I2S) activity was performed on dried blood spot samples submitted for other newborn screening disorders. A positive screen was defined as I2S activity less than or equal to 10% of the daily median. In this series, 28 infants had a positive screening test result, and four other infants had a borderline result. Three positive diagnoses of MPS II were established, and 25 were diagnosed as having I2S pseudodeficiency. The natural history and the clinical features of MPS II make it an ideal target for newborn screening. Newborn screening was effective in identifying affected infants in our population with an acceptable rate of false positive results.

scholarly journals A review of the clinical outcomes in idursulfase-treated and untreated Filipino patients with mucopolysaccharidosis type II: data from the local lysosomal storage disease registry

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Marie Julianne C. Racoma ◽  
Maria Kristina Karizza B. Calibag ◽  
Cynthia P. Cordero ◽  
Mary Ann R. Abacan ◽  
Mary Anne D. Chiong
Keyword(s):  
Adverse Events ◽  
Storage Disease ◽  
Joint Mobility ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Mucopolysaccharidosis Type Ii ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Respiratory Involvement

Abstract Background Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked multisystem disorder characterized by glycosaminoglycan (GAG) accumulation, caused by a deficiency of iduronate-2-sulfatase (I2S). Enzyme replacement therapy (ERT) with recombinant idursulfase (IDS), the standard of care, was started in the Philippines in 2017. This study reviewed the clinical outcomes in idursulfase-treated and untreated Filipino MPS II patients who were included in the local Lysosomal Storage Disease (LSD) registry of the Institute of Human Genetics-National Institutes of Health (IHG-NIH) from January 1999 to December 2019. Methods A retrospective audit of records of MPS II patients listed in the registry was done. Qualified patients were divided into two cohorts: idursulfase-treated group (patients on enzyme replacement therapy, ERT, for ≥ 6 months) and untreated group. Baseline characteristics, including demographic data, biochemical results, neurocognitive classification, respiratory involvement, mortality, and adverse events, were recorded. Height, weight, cardiac pathology, liver and spleen sizes, six-minute walking test (6MWT), joint mobility, were determined at baseline and at year 1 and 2 of follow up. Results Forty male patients were included in this review, with only 8 receiving ERT since 2017. The mean age at diagnosis was 6.99 years (SD 4.15; 0.75–20) and mean age at start of ERT was 14.03 years (SD 7.1; 4–21.5), more delayed than previous reports. Eighty percent have early progressive phenotype which was higher than reported average. The early growth pattern differed in our Filipino cohort, but was followed by the expected slowed growth in later years. Improvements in the following endpoints were observed in the treated cohort: height and weight, cardiac disease, liver and spleen sizes, and joint mobility. There were also positive effects on respiratory involvement and mortality rate. Adverse events were consistent with previous reports. Conclusions ERT is generally well tolerated and effective in reducing GAG storage and improving clinical endpoints among our Filipino MPS II patients. In untreated patients, typical disease progression was observed.

scholarly journals Phenotype Correction in Murine Mucopolysaccharidosis Type VII by Transplantation of Human Amniotic Epithelial Cells after Adenovirus-Mediated Gene Transfer

2000 ◽  
Vol 9 (5) ◽  
pp. 687-692 ◽  
Author(s):  
Motomichi Kosuga ◽  
Satori Takahashi ◽  
Kyoko Sasaki ◽  
Shin Enosawa ◽  
Xiao-Kang Li ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Adenoviral Vectors ◽  
Lysosomal Storage Disorders ◽  
Mucopolysaccharidosis Type ◽  
Lysosomal Storage ◽  
Major Drawback ◽  
Enzyme Replacement ◽  
Murine Fibroblasts ◽  
Human Amniotic Epithelial Cells ◽  
Storage Disorders

Cell therapy with human amniotic epithelial (HAE) cells was developed as an alternative method for enzyme replacement therapy in congenital lysosomal storage disorders, but only limited therapeutic efficacy has been reported. A major drawback is insufficient production and secretion of lysosomal enzymes from HAE cells. In this study, we infected HAE cells with an E1-deleted adenoviral vector expressing human β-glucuronidase (GUSB), and generated cells overexpressing GUSB by a hundred times as much as endogenous GUSB in untreated HAE cells. GUSB secreted from the gene-transferred HAE cells were efficiently transported to murine fibroblasts with endocytosis mediated by mannose-6-phosphate receptors. The cells were administered into the spleen of the mice with the lysosomal storage disease mucopolysaccharidosis type VII (B6/MPSVII). Approximately 10–15% of the normal GUSB activity was detected in both liver and spleen 7 days after the cell administration. Histopathological examination showed that lysosomal enlargement in tissue macrophages in the liver and the spleen had disappeared by day 14. These results suggest that transplantation of the HAE cells transduced with adenoviral vectors can be employed for the treatment of congenital lysosomal storage disorders.

scholarly journals A Review Of The Clinical Outcomes In Idursulfase-Treated And Untreated Filipino Patients With Mucopolysaccharidosis Type II: Data From The Local Lysosomal Storage Disease Registry

2020 ◽  
Author(s):  
Marie Julianne Castillo Racoma ◽  
Maria Kristina Karizza B. Calibag ◽  
Mary Anne D. Chiong ◽  
Mary Ann R. Abacan ◽  
Cynthia Cordero
Keyword(s):  
Adverse Events ◽  
Storage Disease ◽  
Joint Mobility ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Mucopolysaccharidosis Type Ii ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Respiratory Involvement

Abstract Background: Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked multisystem disorder characterized by glycosaminoglycan (GAG) accumulation, caused by a deficiency of iduronate-2-sulfatase (I2S). Enzyme replacement therapy (ERT) with recombinant I2S, the standard of care, was started in the Philippines in 2017. This study reviewed the clinical outcomes in idursulfase-treated and untreated Filipino MPS II patients who were included in the local Lysosomal Storage Disease (LSD) registry of the Institute of Human Genetics-National Institutes of Health (IHG-NIH) from January 1999 to December 2019.Methods: A retrospective audit of records of MPS II patients listed in the registry was done. Qualified patients were divided into two cohorts: idursulfase-treated group (patients on enzyme replacement therapy, ERT, for >6 months) and untreated group. Baseline characteristics, including demographic data, biochemical results, neurocognitive classification, respiratory involvement, mortality, and adverse events, were recorded. Height, weight, cardiac pathology, liver and spleen sizes, six-minute walk test (6MWT), joint mobility, were determined at baseline and at year 1 and 2 of follow up.Results: Forty male patients were included in this review, with 8 receiving ERT since 2017. The mean age at diagnosis was 6.99 years (SD 4.15; 0.75-20) and mean age at start of ERT was 14.03 years (SD 7.1; 4-21.5), more delayed than previous reports. Eighty percent have early progressive phenotype which was higher than reported average. The early growth pattern differed in our Filipino cohort, but was followed by the expected slowed growth in later years. Improvements in the following endpoints were observed in the treated cohort: height and weight, cardiac disease, liver and spleen sizes, and joint mobility. There were also positive effects on respiratory involvement and mortality rate. Adverse events were consistent with previous reports.Conclusions: ERT is generally well tolerated and effective in reducing GAG storage and improving clinical endpoints among our Filipino MPS II patients. In untreated patients, typical disease progression was observed.

scholarly journals Experience of Idursulfase Beta Administration in the Child with Mucopolysaccharidosis Type II: Clinical Case

2020 ◽  
Vol 19 (5) ◽  
pp. 364-370
Author(s):  
Tatiana K. Kruchina ◽  
Konstantin V. Bruchikov ◽  
Gennady A. Novik
Keyword(s):  
Clinical Case ◽  
Storage Disease ◽  
Hunter Syndrome ◽  
Hypersensitivity Reactions ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Mucopolysaccharidosis Type Ii ◽  
Enzyme Replacement ◽  
Mps Ii

Background. Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare hereditary lysosomal storage disease associated with iduronate-2-sulfatase deficiency. Patients with MPS II require life-long enzyme replacement therapy (ERT) to replace the deficiency of endogenous enzyme. There are two medications — idursulfase and idursulfase beta — that are licensed and recommended for these patients in Russian Federation. However, it is well known that ERT can cause hypersensitivity reactions development.Clinical Case Description. The ERT (idursulfase in the dose of 0.5 mg/kg once per week) onset in the male patient with severe MPS II was at the age of 2.5 years. Hypersensitivity reactions (urticaria, fever) were noted incidentally, thus, the premedication with antihistamines and antipyretics was performed. The ERT side effects has aggravated at the age of 8 years despite the glucocorticosteroids admission and infusion rate reduction up to 8–16 ml/h. That is why we have changed the medication on idursulfase beta with major clinical response: we have achieved control on both disease itself and hypersensitivity reactions.Conclusion. The availability of two ERT medications for patients with MPS II expands treatment opportunities. In case of any allergic reactions due to idursulfase, the change on idursulfase beta reduces the risk of any ERT complications with sufficient control of MPS II course.

Pink Rings Lymphocyte: A New Cytologic Abnormality Characteristic of Mucopolysaccharidosis Type II (Hunter Disease)

PEDIATRICS ◽  
1988 ◽  
Vol 82 (2) ◽  
pp. 286-286 ◽  
Author(s):  
MICHELINE MAIER-REDELSPERGER ◽  
MARC-HENRI STERN ◽  
PIERRE MAROTEAUX
Keyword(s):  
Clinical Condition ◽  
Capillary Blood ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Lysosomal Hydrolase ◽  
Pediatric Department ◽  
Hunter Disease ◽  
Leukocyte Morphology ◽  
Storage Disorders

To the Editor.— Mucopolysaccharidoses are a group of rare hereditary storage disorders characterized by various lysosomal hydrolase deficiencies. Clinical condition, radiologic and ophthalmologic examinations, urinary mucopolysaccharides dosage, and leukocyte morphology are generally sufficient for diagnosis.1 However, a more precise classification may be difficult. We herein describe a new lymphocyte abnormality observed in 9/9 cases of type II (Hunter disease) in only 3/19 cases of other types of mucopolysaccharidoses. Capillary blood was collected from 28 children with mucopolysaccharidosis referred to the pediatric department.

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