Newborn screening for primary carnitine deficiency using a second-tier genetic test.

Area of Science:

• Biochemistry
• Genetics
• Neonatal Medicine

Background:

• Newborn screening (NBS) for primary carnitine deficiency (PCD) has suboptimal performance.
• Current screening methods require enhancement for improved diagnostic accuracy.

Purpose of the Study:

• To enhance the efficacy of second-tier genetic screening for PCD.
• To adjust the cutoff value for free carnitine (C0) in NBS.

Main Methods:

• Screened 119,898 neonates for inborn metabolic disorders between January 2021 and December 2022.
• Utilized a novel matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) assay for second-tier genetic screening.
• Selected neonates with C0 levels below 12 μmol/L for further genetic analysis.

Main Results:

• Identified 14 patients diagnosed with PCD among screened neonates.
• The MALDI-TOF MS assay achieved detection and diagnostic rates of 89.29% and 78.57%, respectively.
• Eleven distinct SLC22A5 variants were identified, with c.51C>G being the most common.

Conclusions:

• A novel MALDI-TOF MS assay for 21 SLC22A5 variants was established in a Chinese population.
• The assay demonstrated high detection and diagnostic rates, suitable for population-based genetic screening.
• Combined genetic screening is recommended to improve PCD-NBS efficiency.