Biomarker for Glycogen Storage Diseases (BioGlycogen) (BioGlycogen)

Biomarker for Glycogen Storage Diseases - AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL

Development of a new MS-based biomarker for the early and sensitive diagnosis of Glycogen Storage Diseases from plasma. Testing for clinical robustness, specificity and long-term stability of the biomarker.

Study Overview

• Status: Withdrawn
• Conditions: Fructose Metabolism, Inborn Errors; Glycogen Storage Disease Type II; Glycogen Storage Disease; Glycogen Storage Disease Type V; Glycogen Storage Disease Type I; Glycogen Storage Disease Type III; Glycogen Storage Disease Type VII; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type VI; Glycogen Storage Disease Type VIII

Detailed Description

Glycogen storage diseases (GSDs) are a group of inherited genetic disorders that cause glycogen to be improperly stored in the body. People with glycogen storage diseases have a buildup of abnormal amounts or types of glycogen in their tissues.

The main types of glycogen storage diseases are categorized by number and name. They include:

People with GSD I may have episodes of low blood sugar (hypoglycemia), usually during periods of fasting, due to the ability to store glycogen but inability to properly release it. People with GSD I typically develop an enlarged liver (hepatomegaly) from the storage of glycogen. Elevations in liver function enzymes, blood fat and cholesterol levels, lactic acid, and uric acid also occur. Additional features of GSD I can include decreased bone density, poor growth, kidney disease, liver adenomas, and delayed puberty. Treatment primarily consists of dietary management to maintain normal blood glucose levels and prevent hypoglycemia. GSD I is further divided into subtypes. GSD Type Ia is caused by a deficiency of glucose-6-phosphatase (G6Pase) primarily in the liver, and GSD Type Ib is caused by a deficiency of glucose-6-phosphate translocase. Many of the symptoms are similar, especially early in life. However, some people with Type Ib are more prone to infections given a weaker immune system. GSD I is caused by a non-working change in either the G6PC gene or the SLC37A4 gene, causing the deficiency of the particular enzyme. GSD I follows autosomal recessive inheritance.

Glycogen Storage Disease Type II [also known as Pompe disease, Acid Maltase Deficiency, Glycogenosis Type II, Acid alpha-Glucosidase Deficiency, Lysosomal alpha-Glucosidase Deficiency] Pompe disease is an inherited and often fatal disorder caused by the deficiency of acid alpha-glucosidase (GAA), an enzyme needed to breakdown glycogen (sugar that is stored for energy) in specialized structures in the body, called lysosomes. Patients with Pompe disease have little or no GAA enzyme activity and cannot breakdown glycogen. The excess glycogen accumulates and is stored in the heart, skeletal muscle and other tissues, causing the progressive symptoms of Pompe disease.Glycogen Storage Disease Type III [also known as Cori disease, Forbes disease, Debrancher enzyme deficiency, Limit Dextrinosis]

• Study Type: Observational

Contacts and Locations

Study Locations

• 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 a diagnosis of glycogen storage disease or profound suspicion for glycogen storage disease

Description

Inclusion Criteria:

• Informed consent will be obtained from the parents before any study related procedures.
• Patients of both genders older than 2 month
• The patient has a diagnosis of glycogen storage disease or a high-grade suspicion for glycogen storage disease

High-grade suspicion present, if one or more inclusion criteria are valid:

• Positive family anamnesis for glycogen storage disease
• Hypoglycemia
• Growth retardation: short stature, skeletal myopathy
• Hepatomegaly, Splenomegaly
• Myopathy with muscle weakness
• cardiomyopathy

Exclusion Criteria:

• No Informed consent from the parents before any study related procedures
• Patients of both genders younger than 2 month
• No diagnosis of glycogen storage disease or no valid criteria for high-grade suspicion of glycogen storage 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 a diagnosis of Glycogen storage diseases based upon biochemical and/or genetic criteria or profound suspicion for Glycogen storage 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 Glycogen storage disease using the technique of Mass-spectometry 7,5 ml EDTA blood, saliva tube and a dry blood spot filter card	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: March 2, 2015
• First Submitted That Met QC Criteria: March 10, 2015
• First Posted (ESTIMATE): March 11, 2015

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: Metabolic Diseases; Lysosomal Storage Diseases; Mucolipidoses
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Muscular Dystrophies; Disease; Metabolism, Inborn Errors; Metabolic Diseases; Glycogen Storage Disease Type II; Glycogen Storage Disease; Glycogen Storage Disease Type V; Fructose Metabolism, Inborn Errors; Glycogen Storage Disease Type I; Glycogen Storage Disease Type III; Glycogen Storage Disease Type VII; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type VI; Glycogen Storage Disease Type VIII
• Other Study ID Numbers: BGL 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