Biomarkers for Inborn Errors of Metabolism

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.

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