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Biomarker for Hunter Disease (BioHunt)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2017 by University of Rostock
Centogene AG Rostock
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock Identifier:
First received: April 4, 2011
Last updated: May 3, 2017
Last verified: May 2017
Hunter Syndrome (mucopolysaccharidosis II [MPS II]) is a lysosomal storage disorder caused by reduction or absence of the iduronate-2-sulphatase enzyme has still the problem of the difficulties of a simple and reliable analysis for the primary diagnosis but also for the follow-up of the disease. Especially in the cases of female carriers which have been reported to have some symptoms of MPS II due to skewed X-inactivation makes the diagnosis complex. However, early diagnosis and treatment of disease complications with enzyme replacement therapy can improve quality of life.Therefore the primary aim of our project called "BioHunt" is the development of a new plasma biomarker for the early and sensitive diagnosis of the disease. The secondary aim is the testing for clinical robustness, specificity and long-term stability of the biomarker.Within the scope of the study the investigators would like to collect in the next 12 months from about 80 patient's plasma and in parallel a simple documentation of the clinical data.

Lysosomal Storage Diseases
Hunter Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biomarker for Hunter Disease an International, Multicenter, Epidemiological Protocol

Resource links provided by NLM:

Further study details as provided by University of Rostock:

Primary Outcome Measures:
  • Development of a new MS-based biomarker for the early and sensitive diagnosis of Hunter disease from plasma and saliva [ Time Frame: 24 month ]

Secondary Outcome Measures:
  • Testing for clinical robustness, specificity and long-term stability of the biomarker [ Time Frame: 24 month ]

Biospecimen Retention:   Samples With DNA

After inclusion into the study, blood samples will be drawn to identify a deficiency or absence of the enzyme iduronate-2-sulfatase (I2S).

The laboratory examinations of the blood samples will be done exclusively at the Laboratory of the Albrecht-Kossel-Institute, University of Rostock. This laboratory offers an existing infrastructure, a highly standardized quality of the workflow, a short examination time of the samples and a long period of experiences in the assessment of the biological impact of mutations and polymorphism.

Estimated Enrollment: 80
Study Start Date: March 2011
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Patients from the first day of life with Hunter Disease based upon biochemical and/or genetic criteria or who are profoundly suspicious for Hunter disease

Detailed Description:

Hunter disease (mucopolysaccharidosis type II) is a lysosomal storage disease caused by deficiency of the enzyme iduronate-2-sulphatase. Deficiency of iduronate sulphatase enzyme causes accumulation of the products dermatan sulphate and heparan sulphate in lysosomes leading to cell death. Hunter disease can vary from mild to severe, depending on the level of enzyme deficiency. Features of the disease include dwarfism, enlarged liver and spleen, cardiovascular disorders and deafness.

Mutations in the IDS gene located at Xq28 causes loss of the iduronidate sulfatase enzyme. A pseudogene IDS2 also exists 20 kb from the active IDS gene. The pseudogene IDS2 shares homology to exon 2, intron 2, exon 3, intron 3 and intron 7 of the IDS gene.

Mutations that have been reported in the IDS gene in Hunter patients include gene rearrangements caused by recombination with the IDS2 gene (10 per cent patients), deletions of certain exons or the entire IDS gene (10 per cent patients) or small mutations including insertions, deletions and point mutations (80 per cent patients). To detect all possible types of mutations in the IDS gene causing Hunter disease, three procedures are necessary. These include Southern blot to look for gene rearrangements, multiplex dosage analysis to detect large deletions and DHPLC and sequencing to detect small mutations.

An accurate biochemical test is available for the diagnosis of Hunter disease consisting of the analysis of iduronate-2-sulfatase activity in plasma, leucocytes or cultured cells. This test should be considered before molecular analysis is undertaken. Molecular identification of the mutation in individuals with a confirmed diagnosis can be used for carrier testing and prenatal diagnosis in the family. The biochemical test is not reliable for identifying carriers.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with Hunter Disease based upon biochemical and/or genetic criteria or patients who are profoundly suspicious for Hunter disease

Inclusion Criteria:

  • Informed consent will be obtained from the patient and their parents/legal guardians before any study related procedures.
  • Patients from the first day of life
  • The patient has a diagnosis of Hunter syndrome based upon biochemical and/or genetic criteria or patients who are profoundly suspicious for Hunter disease

High-grade suspicion present, if one or more criteria are valid:

  • Positive family anamnesis for Hunter syndrome
  • Cognitive regression, learning disability or neurocognitive involvement of unrecognized origin
  • Tonic-clonic seizures without identifiable cause
  • Eye symptoms without identifiable cause: corneal clouding or glaucoma
  • Pulmonary symptoms without identifiable cause:

upper airway obstruction, cardiopulmonary disease

Exclusion Criteria:

  • No Informed consent from the patient and their parents/legal guardians before any study related procedures.
  • No diagnosis of Hunter syndrome or no valid criteria for high-grade suspicion of Hunter syndrome
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01330277

Contact: Arndt Rolfs, MD +49 381 494 ext 9540
Contact: Susanne Zielke +49 381 494 ext 4739

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Sponsors and Collaborators
University of Rostock
Centogene AG Rostock
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
  More Information

Additional Information:
Responsible Party: Prof. Dr. Arndt Rolfs, Prof. Dr. med., University of Rostock Identifier: NCT01330277     History of Changes
Other Study ID Numbers: BH03/2011
Study First Received: April 4, 2011
Last Updated: May 3, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by University of Rostock:
Metabolic Diseases
Mucopolysaccharidosis II
Lysosomal Storage Diseases
Morbus Hunter

Additional relevant MeSH terms:
Mucopolysaccharidosis II
Lysosomal Storage Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Connective Tissue Diseases
Metabolic Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System processed this record on May 25, 2017