Clinical trial NCT04098198: Biomarkers for Inborn Errors of Metabolism
Official title: Biomarkers for Inborn Errors of Metabolism: An International, Multicenter, Observational, Longitudinal Protocol
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Inborn Errors of Metabolism
Biomarker
Keywords: Inborn Error of Metabolism
Biomarker
Lead sponsor: CENTOGENE GmbH Rostock
Sponsor class: INDUSTRY
First posted: 2019-09-23
Enrollment: 462
Sex: ALL
Minimum age (years): 2
Maximum age (years): 50
Standard ages: CHILD
ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants with an Inborn Error of Metabolism

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Identification of biomarkers for Inborn Errors of Metabolism
timeFrame: 2 years
Secondary outcomes:
measure: Exploring the clinical robustness, specificity, and long-term variability of biomarkers for Inborn Errors of Metabolism
timeFrame: 2 years
Other outcomes:
Locations:
city: Tirana
country: Albania
facility: University Hospital Center Mother Teresa
city: Alexandria
country: Egypt
facility: Department of Clinical Genetics, Alexandria University Children's Hospital
city: Alexandria
country: Egypt
facility: Department of Pediatrics, Alexandria University Children's Hospital
city: Cairo
country: Egypt
facility: Department of Medical Genetics ,Faculty of Medicine, Ain Shams University
city: Cairo
country: Egypt
facility: Ain Shams University
city: Cairo
country: Egypt
facility: Children's Hospital, Faculty of Medicine, Ain Shams University
city: Tanta
country: Egypt
facility: Pediatrics Departmnet, Tanta University
city: Tbilisi
country: Georgia
facility: Department of Molecular and Medical Genetics , Tbilisi State Medical University
city: Kerola
country: India
facility: Amrita Institute of Medical Sciences
city: Vilnius
country: Lithuania
facility: Children's hospital, Vilnius University Hospital Santaros klinikos
city: Lahore
country: Pakistan
facility: Departmnet of Pediatric Gastroenterology and Hepatology, The Children's Hospital and Institute of Child Health
city: Timişoara
country: Romania
facility: Emergency Hospital for Children "Louis Turcanu"
city: Colombo
country: Sri Lanka
facility: Lady Ridgeway Hospital for Children
Study officials:
affiliation: Centogene GmbH
name: Peter Bauer, Prof. Dr.
role: STUDY_CHAIR
References: