Metabolic

The discovery of biomarkers may open the door to screening newborns for pyridoxine-dependent epilepsy

The door to newborn screening for pyridoxine-dependent epilepsy (PDE), a serious hereditary metabolic disorder, has finally opened. This screening promises better and earlier treatment for the disease.

To identify new biomarkers that can be used in the newborn screening protocol, also known as neonatal heel stitch, researchers from Radboud University Medical Center have teamed up with scientists from Radboud University’s FELIX laser laboratory. They published their results in the Journal of Clinical Investigation.

The discovery and identification of the new biomarkers could lead to an important addition to newborn screening protocols around the world. Over a thousand congenital metabolic disorders (IMD) are currently known, but only 2% of them can be detected by a newborn’s heel stab.

While these are relatively rare as individual illnesses, a child with IMD is born every other day in the Netherlands. These disorders have serious health consequences for patients and are currently a major cause of early child death in the Netherlands.

Technologies combined

Using new techniques in our clinical laboratory, where we study the products of chemical processes (metabolomics), we have been able to detect the presence of compounds in the body fluids of patients that are absent in people who are not affected by PDE – that was a great first step. However, we were only able to identify the exact structure of these compounds, the new PDE biomarkers, with the infrared laser at FELIX. “

Karlien Coene, laboratory specialist and researcher at the Translational Metabolic Laboratory of Radboud University Medical Center, Radboud University Nijmegen

This is the first time an infrared free electron laser – of which there are only a handful in the world – has been combined with these clinical experiments.

Pyridoxine-dependent epilepsy (PDE) is an inherited metabolic disorder characterized primarily by persistent seizures that are unresponsive to conventional anti-epileptic drugs. Seizures are often controlled by high daily doses of vitamin B6, yet 80% of affected children suffer from developmental delays and intellectual disabilities.

Early screening for metabolic diseases is critical to optimal treatment. That’s why researchers are constantly looking for new ways to catch more metabolic diseases earlier in life by the stick. These diseases can be identified by looking for small molecules in the blood that are unique to the disease, also called “biomarkers”.

Avoid bottlenecks

The discovery and identification of biomarkers is a well-known bottleneck in research into metabolic diseases. “In order to overcome this hurdle, we decided to combine the advanced analysis instruments with the infrared laser from the FELIX laboratory,” says Jonathan Martens, researcher at the FELIX laboratory at Radboud University. “The measurements obtained with the unique FELIX laser give us information about the bonds between the atoms and guide us to the exact molecular structure. With this information, we finally managed to synthesize the molecules and thus further investigate their role in the disease. “

In addition to new possibilities in newborn screening, this knowledge has also yielded fundamental knowledge about the disease, which could ultimately lead to optimized treatment and better chances of preventing cognitive disabilities.

Martens: “Now that we have shown that this new combination of techniques really works, we are actively applying our method to research a number of other (metabolic) diseases for which biomarkers are currently lacking.”

Source:

Radboud University of Nijmegen

Journal reference:

Engelke, UFG, et al. (2021) Untargeted metabolomics and infrared ion spectroscopy identify biomarkers for pyridoxine-dependent epilepsy. Clinical Investigation Journal. doi.org/10.1172/JCI148272.

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