Biomarker for Hunter Disease (BioHunt)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01330277
Recruitment Status : Recruiting
First Posted : April 6, 2011
Last Update Posted : August 16, 2018
Information provided by (Responsible Party):
Centogene AG Rostock

Brief Summary:
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.

Condition or disease
Lysosomal Storage Diseases Hunter Disease Mucopolysaccharidoses

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.

Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biomarker for Hunter Disease an International, Multicenter, Epidemiological Protocol
Actual Study Start Date : June 19, 2018
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

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

Primary Outcome Measures :
  1. Development of a new MS-based biomarker for the early and sensitive diagnosis of Hunter disease from plasma and saliva [ Time Frame: 36 month ]

Secondary Outcome Measures :
  1. Testing for clinical robustness, specificity and long-term stability of the biomarker [ Time Frame: 36 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01330277

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

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Hospital de Clinicas de Porto Alegre Recruiting
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University Pediatric Hospital of Sofia Recruiting
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University of Rostck, Albrecht-Kossel-Institute for Neuroregeneration Recruiting
Rostock, Germany, 18147
Contact: Susanne Zielke    +49 381 494 ext 4739   
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Aristotle University of Thessaloniki-Ippokration General Hospital Recruiting
Thessaloniki, Greece, 54642
Contact: Dimitrios Zafeiriou, MD   
Principal Investigator: Dimitrios Zafeiriou, MD         
SOTE Pediatric clinic II, Semmelweis University Recruiting
Budapest, Hungary, 1094
Contact: György Fekete, MD    +36 1 218 ext 6844   
Principal Investigator: György Fekete, MD         
NIRMAN, University of Mumbai Recruiting
Mumbai, India, 400705
Contact: Anil Jalan, MD   
Principal Investigator: Anil Jalan, MD         
Iran, Islamic Republic of
Research center University of Welfare Science, Medical Genetics Department Sarem Women Hospital Recruiting
Teheran, Iran, Islamic Republic of, 13969
Contact: Yousef Shafeghati, MD    +98(21) 44 633 ext 283   
Principal Investigator: Yousef Shafeghati, MD         
The Children's Memorial Health Institute, Department of Metabolic Disease Recruiting
Warsaw, Poland, 04-730
Contact: Anna Tylki-Szymanska, MD    +48 22 815 ext 7066   
Principal Investigator: Anna Tylki-Szymanska, MD         
Mother and Child Health Institute of Serbia- Dr. Vukan Cupic Recruiting
Novi-Beograd, Serbia, 11070
Contact: Adrijan Sarajlija, MD       Adrijan Sarajlija <>   
Principal Investigator: Adrijan Sarajlija, MD         
Sponsors and Collaborators
Centogene AG Rostock
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration

Additional Information:
Responsible Party: Centogene AG Rostock Identifier: NCT01330277     History of Changes
Other Study ID Numbers: BH03/2011
First Posted: April 6, 2011    Key Record Dates
Last Update Posted: August 16, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centogene AG Rostock:
Metabolic Diseases
Mucopolysaccharidosis II
Lysosomal Storage Diseases
Morbus Hunter

Additional relevant MeSH terms:
Lysosomal Storage Diseases
Mucopolysaccharidosis II
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