Biomarker for Hunter Disease (BioHunt)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Rostock
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock
ClinicalTrials.gov Identifier:
NCT01330277
First received: April 4, 2011
Last updated: June 3, 2014
Last verified: June 2014

April 4, 2011
June 3, 2014
March 2011
September 2014   (final data collection date for primary outcome measure)
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Not Provided
Complete list of historical versions of study NCT01330277 on ClinicalTrials.gov Archive Site
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Biomarker for Hunter Disease
Biomarker for Hunter Disease an International, Multicenter, Epidemiological Protocol

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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

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.

Probability Sample

Patients with Hunter Disease based upon biochemical and/or genetic criteria or patients who are profoundly suspicious for Hunter disease

  • Lysosomal Storage Diseases
  • Hunter Disease
  • Mucopolysaccharidoses
Not Provided
Observation
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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
October 2014
September 2014   (final data collection date for primary outcome measure)

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
Both
Not Provided
No
Contact: Arndt Rolfs, MD +49 381 494 ext 9540 arndt.rolfs@med.uni-rostock.de
Contact: Susanne Zielke +49 381 494 ext 4739 susanne.zielke@med.uni-rostock.de
Algeria,   Brazil,   Bulgaria,   Germany,   Greece,   Hungary,   India,   Iran, Islamic Republic of,   Poland,   Serbia
 
NCT01330277
BH03/2011
Yes
Prof. Dr. Arndt Rolfs, University of Rostock
University of Rostock
Not Provided
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
University of Rostock
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP