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

Biomarker for Sly Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL

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

Study Overview

• Status: Withdrawn
• Conditions: Developmental Delay; Splenomegaly; Hepatomegaly; Skeletal Abnormalities

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 Type: Observational

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 89075
    • Children's Hospital, Faculty of Medicine, Ain Shams University
• Germany
  • Rostock, Germany, 18055
    • Centogene AG
• India
  • Mumbai, India, 400705
    • Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN)
  • Kerala
    • Cochin, Kerala, India, 682041
      • Amrita Institute Of Medical Sciences & Research Centre
• Sri Lanka
  • Colombo 8, Sri Lanka, 00800c
    • Lady Ridgeway Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CENTOGENE GmbH Rostock

Publications and helpful links

Helpful Links

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 20, 2018
• Primary Completion (ACTUAL): February 28, 2021
• Study Completion (ACTUAL): February 28, 2021

Study Registration Dates

• First Submitted: October 23, 2014
• First Submitted That Met QC Criteria: November 19, 2014
• First Posted (ESTIMATE): November 24, 2014

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Biomarker; Sly Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Liver Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Pathological Conditions, Anatomical; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Hypertrophy; Splenomegaly; Hepatomegaly; Mucopolysaccharidosis VII
• Other Study ID Numbers: BSLY 06-2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No