Newborn Screening for Familial Hypercholesterolemia Using Liquid Chromatography Tandem Mass Spectrometry-Based Free...

Area of Science:

• Neonatal screening
• Biomarker discovery
• Lipid metabolism

Background:

• Familial hypercholesterolemia (FH) is a genetic disorder leading to premature cardiovascular disease.
• Early diagnosis and treatment of FH are crucial for preventing long-term health complications.
• Current newborn screening methods may not adequately identify all cases of FH.

Purpose of the Study:

• To assess the feasibility of measuring free cholesterol (FC) in dried blood spots (DBS) from newborns.
• To evaluate the potential of FC as a screening marker for lipid abnormalities, including FH.
• To pilot FC measurement within a newborn screening program in the Euroregion Pomerania.

Main Methods:

• Analysis of DBS samples from 7,973 newborns participating in the RareScreen project.
• Quantification of FC concentration using liquid chromatography tandem mass spectrometry (LC-MS/MS).
• Examination of FC concentration distribution and potential influencing factors.

Main Results:

• FC concentrations in DBS ranged from 0.005 to 1.521 mmol/L (0.19 to 58.89 mg/dL).
• No significant impact of newborn sex, gestational age, birth weight, or sampling age on FC levels was observed.
• The 99.5th percentile for FC concentration was determined to be 1.159 mmol/L (44.8 mg/dL).

Conclusions:

• Large-scale FC measurement in neonatal DBS using LC-MS/MS is feasible in a central laboratory setting.
• FC levels were found to be consistent across various demographic and clinical newborn characteristics.
• FC shows promise as a novel screening marker for lipid abnormalities, warranting further validation in future studies.