Biomarker for Sly Disease (MPS VII) (BioSly)

Study Overview
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Brief Summary
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Development of a new MS-based biomarker for the early and sensitive diagnosis of Sly disease from blood (plasma)

Detailed Description
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Mucopolysaccharidosis type VII (also known as Sly syndrome or Sly disease) is an inherited disease caused by a lack of the enzyme beta-glucuronidase. This enzyme is needed to break down substances in the body called glycosaminoglycans (GAGs). If the enzyme is not present, GAGs cannot be broken down and they build up in the cells and damage them. This causes a wide range of problems such as short stature, skeletal abnormalities, joint stiffness, enlarged spleen and liver, lung infections, heart problems and hernias. Patients usually die within the first year of life, although some survive into their teenage years. Mucopolysaccharidosis type VII is a life-threatening disease with many patients dying in early childhood. It also debilitating due to the physical and skeletal abnormalities that occur. Sly syndrome is characterized by coarse facial features, hepatosplenomegaly, protruding sternum and dystosis multiplex. Dystosis multiplex refers to a constellation of skeletal abnormalities and is characterized by an enlarged skull, thickened calvarium, premature closure of lamboid and sagittal sutures, shallow orbits, enlarged J-shaped sella and abnormal spacing of the teeth with dentigerous cysts. There is anterior hypoplasia of the lumbar vertebrae, the long bone diaphyses are enlarged and an irregular appearance of the metaphyses. The epiphyseal centers not well developed, the pelvis is poorly formed with small femoral heads and coxa valga. The clavicles are short, thick and irregular and the ribs are oar shaped. Phalanges are shortened and trapezoidal in shape. At the time of designation, mucopolysaccharidosis type VII affected approximately 0.001 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 50 people, and is below the ceiling for orphan designation, which is 5 people in 10,000. New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood (plasma) of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity. Therefore it is the goal of the study to identify and validate a new biochemical marker from the plasma of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.

Official Title
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Biomarker for Sly Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL

Conditions
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Developmental Delay, Skeletal Abnormalities, Hepatomegaly, Splenomegaly

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Informed consent will be obtained from the parents before any study related procedures Patients of both genders older than 2 months The patient has a diagnosis of Sly disease or a high-grade suspicion for Sly disease High-grade suspicion present, if one or more inclusion criteria are valid: Positive family anamnesis for Sly disease Developmental delay and/or progressive mental deterioration Skeletal abnormalities Hepatomegaly Splenomegaly EXCLUSION CRITERIA: No Informed consent from the parents before any study related procedures. Patients of both genders younger than 2 months No diagnosis of Sly disease or no valid criteria for profound suspicion of Sly disease

Ages Eligible for Study
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Minimum Age: 2 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observation<br>Patients with Sly disease or high-grade suspicion for Sly disease | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of a new MS-based biomarker for the early and sensitive diagnosis of Sly disease from blood (plasma) | New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Testing for clinical robustness, specificity and long-term stability of the biomarker | the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sly Disease, Biomarker