Biomarkers for Inborn Errors of Metabolism (BioMetabol)

Biomarkers for Inborn Errors of Metabolism: An International, Multicenter, Observational, Longitudinal Protocol

International, multicenter, observational, longitudinal study to identify or monitor Inborn Error of Metabolism disease biomarkers and to explore the clinical robustness, specificity, and long-term variability of these biomarkers

Study Overview

• Status: Completed
• Conditions: Inborn Errors of Metabolism; Biomarker

Detailed Description

Inborn Errors of Metabolism (IEM) are a large group of congenital metabolic disorders, resulting from the absence or abnormality of an enzyme or its cofactor and leading to either accumulation or deficiency of a specific metabolite. More than 800 IEM have been described in the literature, with a widely accepted classification focusing on the main substrate which is affected.

Clinical phenotypes of IEM are broad and often non-specific, mimicking more common conditions, and the onset of symptoms can occur at any age, from fetus to adult. Peroxisomal and lysosomal storage disorders, for example, often have characteristic clinical features and permanent, progressive symptoms that are independent of triggering events (e.g. anemia, thrombocytopenia, and hepatomegaly in a child of Ashkenazi-Jewish ancestry is suggestive of Gaucher disease) 6. More common findings include hypoketotic hypoglycemia, lactic acidosis, metabolic acidosis, ketosis, hyperammonemia, or other metabolic acidosis in combination with hyperammonemia.

The goal of treatment for participants with IEM are the prevention of further accumulation of harmful substances, correction of metabolic abnormalities, and elimination of toxic metabolites. Most participants suffering for rare metabolic diseases start with very severe phenotypes and with rapid progression of the disease that often leads to irreversible damage of their organs. A quick diagnosis is necessary for urgent treatment.

Biomarkers serve as measurable indicators of normal biological or pathological processes. They are typically directly linked to genetic variants in specific genes and can predict, diagnose, monitor and assess the severity of a disease.

CENTOGENE has an outstanding experience regarding the investigation and development of biomarkers for IEM. Given the large amount of participants CENTOGENE is facing and diagnosing, it has a big repertoire of samples to use for the biomarker characterization. This led for example to the identification of Lyso-Gb1 as a novel biomarker for Gaucher disease orLyso-SM509 for Niemann-Pick Disease. The established workflows and gained knowledge for the biomarker development at CENTOGENE will enhance the search for new biomarkers of other IEM.

It is the goal of this study to identify, validate, and monitor biochemical markers from affected participants for Inborn Errors of Metabolism.

• Study Type: Observational
• Enrollment (Actual): 462

Contacts and Locations

Study Locations

• Albania
  • Tirana, Albania, 10001
    • University Hospital Center Mother Teresa
• Egypt
  • Alexandria, Egypt, 21131
    • Department of Clinical Genetics, Alexandria University Children's Hospital
  • Alexandria, Egypt, 21131
    • Department of Pediatrics, Alexandria University Children's Hospital
  • Cairo, Egypt
    • Ain Shams University
  • Cairo, Egypt, 11566
    • Department of Medical Genetics ,Faculty of Medicine, Ain Shams University
  • Cairo, Egypt
    • Children's Hospital, Faculty of Medicine, Ain Shams University
  • Tanta, Egypt, 31527
    • Pediatrics Departmnet, Tanta University
• Georgia
  • Tbilisi, Georgia, 0177
    • Department of Molecular and Medical Genetics , Tbilisi State Medical University
• India
  • Kerola, India, 682041
    • Amrita Institute of Medical Sciences
• Lithuania
  • Vilnius, Lithuania, O8406
    • Children's hospital, Vilnius University Hospital Santaros klinikos
• Pakistan
  • Lahore, Pakistan, 54600
    • Departmnet of Pediatric Gastroenterology and Hepatology, The Children's Hospital and Institute of Child Health
• Romania
  • Timişoara, Romania, 300011
    • Emergency Hospital for Children "Louis Turcanu"
• Sri Lanka
  • Colombo, Sri Lanka, 00800
    • Lady Ridgeway Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 50 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants with an Inborn Error of Metabolism

Description

Inclusion Criteria:

• Informed consent is obtained from the participant or from their parent/legal guardian, before any study related procedures
• The participant aged between 2 months old and 50 years old
• The diagnosis of an Inborn Error of Metabolism is genetically confirmed

Exclusion Criteria:

• Inability to provide informed consent
• The participant is younger than 2 months old or older than 50 years old
• The diagnosis of an Inborn Error of Metabolism (IEM) is not genetically confirmed
• Previously enrolled in the study

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
Participants with an Inborn Error of Metabolism; Participants diagnosed with an Inborn Error of Metabolism aged between 2 months to 50 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of biomarkers for Inborn Errors of Metabolism	All samples will be analyzed for the identification of biomarker/s via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploring the clinical robustness, specificity, and long-term variability of biomarkers for Inborn Errors of Metabolism	Samples will be analyzed for the identified biomarker candidates via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.	2 years

Collaborators and Investigators

• Sponsor: CENTOGENE GmbH Rostock

Publications and helpful links

Helpful Links

• CENTOGENE is a rare disease company focused on transforming clinical, genetic, and biochemical data into medical solutions for patients

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): March 11, 2022
• Study Completion (Actual): March 11, 2022

Study Registration Dates

• First Submitted: August 23, 2019
• First Submitted That Met QC Criteria: September 18, 2019
• First Posted (Actual): September 23, 2019

Study Record Updates

• Last Update Posted (Actual): March 24, 2022
• Last Update Submitted That Met QC Criteria: March 23, 2022
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Biomarker; Inborn Error of Metabolism
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors
• Other Study ID Numbers: BioMetabol

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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