Biomarker for Sly Disease (MPS VII) (BioSly)

Sponsor

CENTOGENE GmbH Rostock (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02298699

Collaborator

(none)

1,000

Enrollment

Locations

35.4

Anticipated Duration (Months)

200

Patients Per Site

5.7

Patients Per Site Per Month

Study Details

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	Intervention/Treatment	Phase
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

Anticipated Enrollment :

1000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Biomarker for Sly Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL

Actual Study Start Date :

Aug 20, 2018

Anticipated Primary Completion Date :

Aug 1, 2021

Anticipated Study Completion Date :

Aug 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Observation Patients with Sly disease or high-grade suspicion for Sly disease

Outcome Measures

Primary Outcome Measures

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

Testing for clinical robustness, specificity and long-term stability of the biomarker [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Months and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	Children's Hospital, Faculty of Medicine, Ain Shams University	Cairo		Egypt	89075
2	Centogene AG	Rostock		Germany	18055
3	Amrita Institute of Medical Sciences & Research Centre	Cochin	Kerala	India	682041
4	Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN)	Mumbai		India	400705
5	Lady Ridgeway Hospital for Children	Colombo 8		Sri Lanka	00800c