Biomarker for Hunter Disease (BioHunt)

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.

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

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