Expanded newborn screening program in Slovenia using tandem mass spectrometry and confirmatory next generation sequencing genetic testing
, , , , , , , , , , , , and | Oct 18, 2020
About this article
Article Category: Research Article
Published Online: Oct 18, 2020
Page range: 256 - 263
Received: Apr 17, 2020
Accepted: Sep 17, 2020
DOI: https://doi.org/10.2478/sjph-2020-0032
Keywords
© 2020 National Institute of Public Health, Slovenia
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
Figure 1
Figure 2
Panel of 72 genes for the NGS confirmatory testing in expanded NBS program.
| ABCD1 | ABCD4 | ACAD8 | ACAD9 | ACADL | ACADM | ACADS | ACADVL |
| ACAT1 | ADA | ALDH18A1 | ARG1 | ASL | ASS | AUH | BCAT2 |
| BCKDHA | BCKDHB | BTD | CD320 | CPS1 | CPT1A | CPT2 | DBT |
| DLD | ETFA | ETFB | ETFDH | ETHE1 | FAH | GCDH | GCH1 |
| GLUL | HADH | HADHA | HADHB | HLCS | HMGCL | HMGCS2 | HPD |
| HSD17B10 | IVD | LMBRD1 | MCCC1 | MCCC2 | MLYCD | MMAA | MMAB |
| MMACHC | MMADHC | MTR | MTRR | MMUT | NAGS | OTC | PAH |
Values of acylcarnitines and amino acids at newborn screening and follow-up for confirmed patients. CoA – coenzyme A, DBS – dried blood spot, NBS – newborn screening, ref. – reference.
| Module name | NBS results (from DBS) μmol/L | Follow-up (from DBS) μmol/L | Confirmation tests |
|---|---|---|---|
| C14:1: 3.41 (˂0.32) C14: 1.41 (˂0.42) C14:2: 0.44 (0–0.05) C14:1/C2: 0.200 (˂0.014) C14:1/C16: 0.84 (˂0.08) | C14:1: 0.84 (˂0.32) C14: 0.41 (˂0.42)C14:2: 0.18 (˂0.05) C14:1/C2: 0.090 (˂0.014) C14:1/C16: 0.31 (˂0.08) | One known heterozygous pathogenic variant and one likely pathogenic variant | |
| C5: 2.47 (˂0.28) C5/C0: 0.132 (˂0.018) C5/C2: 0.164 (˂0.017) C5/C3: 1.91 (˂0.21) | C5: 5.77 (˂0.28) C5/C0: 0.222 (˂0.018) C5/C2: 0.499 (˂0.017) C5/C3: 5.84 (˂0.21) | Elevated isovalerylglycine in urine Reduced enzyme activity: 0.1 nmol/(min mg prot) (ref. value: 0.94–1.94) | |
| C8: 0.27 (˂0.16) C6: 0.27 (˂0.12) C10: 0.11 (˂0.26) C10:1: 0.13 (˂0.09) C8/C10: 2.45 (˂1.50) C8/C2: 0.07 (0.01) | C8: 0.96 (˂0.27) C6: 0.477 (˂0.15) C10: 0.14 (˂0.32) C10:1: 0.285 (˂0.25) C8/C10: 6.8 (˂2.3) C8/C2: 0.07 (0.02) | One known heterozygous pathogenic variant and one variant of unknown significance Reduced enzyme activity: 0.20 nmol/(min mg prot) (ref. value: 0.43–1.63) | |
| Proline: 623 (˂261) | Proline: 794 (˂441) | Two pathogenic variants. |
|
List of diseases included in expanded NBS program. * – already running newborn screening program for phenylketonuria; in agreement, the program is running in parallel for two years on both systems, and the reported results are from the existing program for PKU screening.
| Tyrosinemia type 1 | Carnitine palmitoyltransferase deficiency type 2 |
| Maple syrup urine disease | 3-methylcrotonyl-CoA carboxylase deficiency |
| Isovaleric acidemia | 3-hydroxy-3-methylglutaric aciduria |
| Glutaric aciduria type 1 | Holocarboxylase synthethase deficiency |
| Glutaric aciduria type 2 | β-ketothiolase deficiency |
| Propionic aciduria | Very long-chain acyl-CoA dehydrogenase deficiency |
| Methylmalonic aciduria | Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency |
| Carnitine uptake deficiency | Medium-chain acyl-CoA dehydrogenase deficiency |
| Carnitine palmitoyltransferase deficiency type 1 | Phenylketonuria* |