Assessment and Application of Acylcarnitines Summations as Auxiliary Quantization Indicator for Primary Carnitine...

Area of Science:

• Biochemistry
• Metabolic Disorders
• Newborn Screening

Background:

• Newborns with low free carnitine (C0) are referred for primary carnitine deficiency (PCD) testing.
• Current screening methods lead to a high rate of false-positive referrals.

Purpose of the Study:

• To evaluate acylcarnitines and their summations for improving PCD diagnostic accuracy.
• To reduce false-positive referrals in newborn screening for PCD.

Main Methods:

• Retrospective analysis of 72 genetically confirmed PCD cases.
• Validation of C0 with butyrylcarnitine (C4) + isovalerylcarnitine (C5) in ~80,000 samples.
• Utilized ROC curve analysis to assess discriminant power.

Main Results:

• C4, acetylcarnitine (C2), and C5 showed high discriminant power (AUC >98%) for PCD.
• The C4 + C5 summation achieved 100% sensitivity at a cutoff of 0.181 μmol/L.
• In validation, C4 + C5 addition increased positive predictive value (PPV) from 0.75% to 1.54% in newborn screening.

Conclusions:

• C4 and C5 are ideal auxiliary indicators for improving PCD diagnosis.
• The C4 + C5 summation effectively reduces false-positive results in PCD screening.
• Recommended use of C4 + C5 as an auxiliary indicator for PCD follow-up.