Biomarker for Sly Disease (MPS VII) (BioSly) (BioSly)

• ClinicalTrials.gov Identifier: NCT02298699
• Recruitment Status: Active, not recruiting
• First Posted: November 24, 2014
• Last Update Posted: April 3, 2020
• Sponsor: Centogene AG Rostock
• Information provided by (Responsible Party): Centogene AG Rostock

Study Description

Brief Summary:

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

Condition or disease
Developmental Delay; Skeletal Abnormalities; Hepatomegaly; Splenomegaly

Detailed Description:

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 1000 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Biomarker for Sly Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL
• Actual Study Start Date: August 20, 2018
• Estimated Primary Completion Date: August 2021
• Estimated Study Completion Date: August 2021

Groups and Cohorts

Group/Cohort
Observation; Patients with Sly disease or high-grade suspicion for Sly disease

Outcome Measures

Primary Outcome Measures :

1. Development of a new MS-based biomarker for the early and sensitive diagnosis of Sly disease from blood (plasma) [ Time Frame: 24 months ]
   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.

Secondary Outcome Measures :

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

Biospecimen Retention:   Samples With DNA

For the development of the new biomarkers using the technique of Mass-spectometry 10 ml EDTA blood and a dry blood spot filter card are taken. To proof the correct Sly diagnosis in those patients where up to the enrolment in the study no genetic testing has been done, sequencing of Sly will be done. The analyses will be done at:

Centogene AG Am Strande 7 18055 Rostock Germany

Eligibility Criteria

• Ages Eligible for Study: 2 Months and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Patients with Sly disease or high-grade suspicion for Sly disease

Criteria

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

Contacts and Locations

Locations

Egypt

Children's Hospital, Faculty of Medicine, Ain Shams University

Cairo, Egypt, 89075

Germany

Centogene AG

Rostock, Germany, 18055

India

Amrita Institute of Medical Sciences & Research Centre

Cochin, Kerala, India, 682041

Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN)

Mumbai, India, 400705

Sri Lanka

Lady Ridgeway Hospital for Children

Colombo 8, Sri Lanka, 00800c

Sponsors and Collaborators

Centogene AG Rostock

Investigators

• Principal Investigator: Arndt Rolfs, Prof.; Centogene AG Rostock

More Information

Additional Information:

Centogene is one of the leading laboratories focusing on genetic testing for rare hereditary disorders. We now offer more than 2200 routine genetic and biochemical tests. 

• Responsible Party: Centogene AG Rostock
• ClinicalTrials.gov Identifier: NCT02298699
• Other Study ID Numbers: BSLY 06-2018
• First Posted: November 24, 2014
• Last Update Posted: April 3, 2020
• Last Verified: April 2020

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:

Sly Disease; Biomarker

Additional relevant MeSH terms:

Hepatomegaly; Mucopolysaccharidosis VII; Splenomegaly; Hypertrophy; Pathological Conditions, Anatomical; Liver Diseases; Digestive System Diseases; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Metabolic Diseases