Discovery of biomarkers may open the door to screening for pyridoxine-dependent epilepsy in newborns


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

To identify new biomarkers that can be used in the newborn screening protocol, also known as the neonatal heel prick, researchers at Radboud University Medical Center have teamed up with scientists from the FELIX laser lab at Radboud University. They published their findings in The Clinical investigation journal.

The discovery and identification of new biomarkers could lead to an important addition to global newborn screening protocols. Currently, there are over a thousand known innate metabolic diseases (IMDs), but only 2% of them can be detected by the neonatal heel prick.

Although these disorders are relatively rare as individual disorders, in the Netherlands a child is born every other day with IMD. These disorders have serious consequences for the health of patients and are currently one of the leading causes of early death in children in the Netherlands.

Combined technologies

Using new techniques in our clinical laboratory where we study the products of chemical (metabolomic) processes, we were able to detect the presence of compounds in the body fluids of patients that are not present in people not affected by PDE – c ‘was an important first step. However, we were only able to identify the exact structure of these compounds, the new PDE biomarkers, using the FELIX infrared laser.. “

Karlien Coene, Laboratory Specialist and Researcher at the Translational Metabolic Laboratory at Radboud University Medical Center, Radboud University of Nijmegen

This is the first time that a free electron infrared laser – of which there is only one hand full in the world – has been associated with these clinical experiments.

Pyridoxine-dependent epilepsy (PDE) is an inherited metabolic disorder that is characterized primarily by intractable seizures that do not respond to conventional anti-epileptic drugs. Seizures are often controlled by high daily doses of vitamin B6, however 80% of affected children still suffer from developmental delay and intellectual disability.

Early detection of metabolic diseases is essential for optimal treatment. That’s why researchers are constantly looking for new ways to detect more metabolic diseases earlier in life via the heel prick. These diseases can be identified by looking for the presence in the blood of small disease-specific molecules, also called “biomarkers”.

Bypass bottlenecks

The discovery and identification of biomarkers is a well-known bottleneck in metabolic disease research. “To overcome this obstacle, we decided to combine advanced analytical instrumentation with the infrared laser from the FELIX laboratory,” explains Jonathan Martens, researcher at the FELIX laboratory at Radboud University. “The measurements obtained using the unique FELIX laser tell us about the links. between atoms and leads us to the precise molecular structure. Thanks to this information, we were finally able to synthesize the molecules and this allowed us to deepen their research on their role in the disease. “

In addition to new possibilities for newborn screening, this discovery also revealed fundamental information about the disease, which could ultimately lead to optimized treatment and a better chance of preventing cognitive impairment.

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


Journal reference:

Engelke, UFG, et al. (2021) Non-target metabolomics and infrared ion spectroscopy identify biomarkers of pyridoxine-dependent epilepsy. Clinical investigation journal.


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