Newborn Screening with (C16 + C18:1)/C2 and C14/C3 for Carnitine Palmitoyltransferase II Deficiency throughout Japan Has Revealed C12/C0 as an Index of Higher Sensitivity and Specificity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Screening Test for CPT II Deficiency
2.2. Confirmatory Tests for CPT II Deficiency
2.3. Receiver Operating Characteristic Analysis
3. Results
3.1. Diagnoses of NBS Positivity and Levels of the Current Indices
3.2. Patients with Symptoms of CPT II Deficiency but Normal NBS Results
3.3. Comparison of (C16 + C18:1)/C2 and C14/C3 with Various Acylcarnitines and Their Ratios
3.4. Results of Serum Acylcarnitine Analysis at the First Medical Examination
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Groups and Descriptions | n | Case ID * | CPT II Activity |
---|---|---|---|
Group A: NBS-positive, patients with CPT II deficiency | 21 | S-01, N-01 to N-20 | 1.2–27.9% |
Group B-1: NBS-positive, carriers heterozygous for pathogenic CPT2 variants | 2 | N-21, N-37 | 31.8%, 70.8% |
Group B-2: NBS-positive, homozygous for p.F352C | 3 | N-22, N-26, N-35 | 34.0%, 52.0%, 63.8% |
Group B-3: NBS-positive, CPT II activity between 31.8% and 70.8% without genetic confirmation of either heterozygosity for pathogenic variants or homozygosity for p.F352C | 12 | N-23 to N-25, N-27 to N-34, N-36 | 37.7–67.4% |
Group C: NBS-positive infants with normal-level CPT II activity | 33 | N-38 to N-70 | 78.1–410.4% (mean value = 152.2% ± 83.8%) |
Group D: Patients with symptoms of CPT II deficiency but normal results in NBS | 5 | S-02 to S-06 | 8.1–30.2% |
Characteristic | Acylcarnitine and Free Carnitine (C0) Levels | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
C16 | C18:1 | C18 | C16-OH | C14 | C14:1 | C12 | C10 | C8 | C6 | C4 | C3 | C2 | C0 | |
Optimal cutoff (nmol/mL) | 9.8 | 2.56 | 1.695 | 0.027 | 0.295 | 0.106 | 0.155 | 0.085 | 0.095 | 0.02 | 0.111 | 0.55 | 5.61 | 20.225 |
Sensitivity | 0.231 | 0.346 | 0.308 | 0.600 | 0.640 | 0.400 | 0.885 | 0.846 | 0.192 | 0.696 | 0.750 | 0.808 | 0.769 | 0.885 |
Specificity | 1 | 0.980 | 0.980 | 0.872 | 0.900 | 0.851 | 0.938 | 0.646 | 0.917 | 0.425 | 0.475 | 0.480 | 0.640 | 0.620 |
Area under the curve | 0.526 | 0.576 | 0.603 | 0.727 | 0.822 | 0.644 | 0.960 | 0.784 | 0.524 | 0.526 | 0.600 | 0.622 | 0.706 | 0.733 |
Characteristic | Acylcarnitine Ratios | |||||||
---|---|---|---|---|---|---|---|---|
(C16 + C18:1)/C2 | C14/C3 | C14/C2 | C14/C0 | C12/C2 | C12/C0 | C10/C2 | C10/C0 | |
Optimal cutoff | 0.857 | 0.620 | 0.066 | 0.018 | 0.020 | 0.008 | 0.017 | 0.005 |
Sensitivity | 0.577 | 0.800 | 0.760 | 0.800 | 0.885 | 0.962 | 0.808 | 0.962 |
Specificity | 0.940 | 0.780 | 1 | 0.940 | 0.979 | 0.958 | 0.896 | 0.667 |
Area under the curve | 0.698 | 0.766 | 0.832 | 0.908 | 0.932 | 0.981 | 0.895 | 0.885 |
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Tajima, G.; Hara, K.; Tsumura, M.; Kagawa, R.; Sakura, F.; Sasai, H.; Yuasa, M.; Shigematsu, Y.; Okada, S. Newborn Screening with (C16 + C18:1)/C2 and C14/C3 for Carnitine Palmitoyltransferase II Deficiency throughout Japan Has Revealed C12/C0 as an Index of Higher Sensitivity and Specificity. Int. J. Neonatal Screen. 2023, 9, 62. https://doi.org/10.3390/ijns9040062
Tajima G, Hara K, Tsumura M, Kagawa R, Sakura F, Sasai H, Yuasa M, Shigematsu Y, Okada S. Newborn Screening with (C16 + C18:1)/C2 and C14/C3 for Carnitine Palmitoyltransferase II Deficiency throughout Japan Has Revealed C12/C0 as an Index of Higher Sensitivity and Specificity. International Journal of Neonatal Screening. 2023; 9(4):62. https://doi.org/10.3390/ijns9040062
Chicago/Turabian StyleTajima, Go, Keiichi Hara, Miyuki Tsumura, Reiko Kagawa, Fumiaki Sakura, Hideo Sasai, Miori Yuasa, Yosuke Shigematsu, and Satoshi Okada. 2023. "Newborn Screening with (C16 + C18:1)/C2 and C14/C3 for Carnitine Palmitoyltransferase II Deficiency throughout Japan Has Revealed C12/C0 as an Index of Higher Sensitivity and Specificity" International Journal of Neonatal Screening 9, no. 4: 62. https://doi.org/10.3390/ijns9040062