Table 2.
LC-MS/MS assays currently used in NBS laboratories or pilot studies associated with the authors.1.
| Disorder(s) | Marker(s) | Method | First or Second- Tier Test |
Comments |
|---|---|---|---|---|
| MPS, all types [11,12,13] | glycosaminoglycans | LC-MS/MS | second | All NBS labs contract with another lab, except in Italy [18] |
| MPS-I | α-iduronidase activity |
FIA-MS/MS or LC-MS/MS |
first | NBS labs in the USA, Taiwan, the Netherlands and regions of Italy use FIA-MS/MS, except Illinois [19] and Utah, which use LC-MS/MS |
| MPS-II | iduronate-2-sulfatase activity |
LC-MS/MS | first | Illinois [20], Taiwan, ScreenPlus (pilot) |
| MPS-IIIA | heparan N-sulfatase activity |
LC-MS/MS | first | ScreenPlus (pilot) |
| MPS-IIIB | α-N-acetyl- glucosaminidase activity |
LC-MS/MS | first | 2/3 of Taiwan, ScreenPlus (pilot) |
| MPS-IVA | galactosamine-6-sulfatase activity | LC-MS/MS | first | Taiwan, ScreenPlus (pilot) |
| MPS-IVB/ GM1-gangliosidosis |
β-galactosidase activity | LC-MS/MS | first | ScreenPlus (pilot) |
| MPS-VI | arylsulfatase B activity | LC-MS/MS | first | Taiwan, ScreenPlus (pilot) |
| MPS-VII | β-glucuronidase activity | LC-MS/MS | first | ScreenPlus (pilot) |
| X-ALD [21,22] | C26-lysophosphatidylcholine | LC-MS/MS or FIA-MS/MS |
first- and second-tier |
The Netherlands, Taiwan. Connecticut, Illinois, Minnesota, Missouri, North Carolina (pilot), Utah, Washington and 2/3 of Taiwan use first-tier LC-MS/MS; all other US labs use second-tier LC-MS/MS |
| Krabbe disease | galactosylcerebrosidase activity |
FIA-MS/MS or LC-MS/MS |
first | Georgia (Pilot), Illinois, Indiana, Kentucky, New York, Ohio, Pennsylvania and Tennessee all use FIA-MS/MS, except Illinois uses LC-MS/MS |
| Krabbe disease [15,23] | Psychosine | LC-MS/MS | second | Most but not all NBS labs obtain second-tier tests through a contract with another laboratory |
| Pompe disease | acid α-glucosidase activity |
FIA-MS/MS or LC-MS/MS |
first | ~50% of NBS labs in the USA, 2/3 of Taiwan and regions of Italy all use FIA-MS/MS, except Illinois and 1/3 of Taiwan use LC-MS/MS |
| Fabry disease | α-galactosidase A activity |
FIA-MS/MS or LC-MS/MS |
first | Tennessee, New Jersey, Pennsylvania, regions of Italy and 2/3 of Taiwan use FIA-MS/MS; Illinois and 1/3 of Taiwan use LC-MS/MS |
| Fabry disease | globotriaosyl- sphingosine |
LC-MS/MS | second | Used but not relied upon in Italy because it is only abnormal in classic Fabry disease [18]; ScreenPlus (pilot) |
| Niemann-Pick A/B | acid sphingomyelinase activity |
LC-MS/MS | first | Illinois, regions of Italy [18], ScreenPlus (pilot) |
| Niemann-Pick A/B | lysosphingomyelin, N-palmitoyl-O-phosphocholine-serine (lyso-SM-509) |
LC-MS/MS | second | ScreenPlus (pilot); primarily available through a contract with another laboratory |
| Gaucher | β-Glucocerebrosidase activity |
FIA-MS/MS or LC-MS/MS |
first | Illinois, ScreenPlus (pilot) and 1/3 of Taiwan use LC-MS/MS; New Jersey, Pennsylvania, Tennessee, regions of Italy and 2/3 of Taiwan use FIA-MS/MS |
| Gaucher | glucosylsphingosine | LC-MS/MS | second | Italy [18], ScreenPlus (pilot); primarily available through a contract with another laboratory |
| Congenital adrenal hyperplasia [9,10,24] | 17-hydroxy- progesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol, cortisol |
LC-MS/MS | second | Primarily available through a contract with another laboratory |
| Maple syrup urine disease [25] | allo-isoleucine, isoleucine, leucine, valine, hydroxyproline | LC-MS/MS | second | Primarily available through a contract with another laboratory |
| Propionic acidemia/methylmalonic acidemias/homocystinuria/ remethylation disorders [16,26,27] |
methylmalonic acid, methylcitric acid, total homocysteine, 3-hydroxypropionic acid |
LC-MS/MS | second | Primarily available through a contract with another laboratory |
| SCAD/GA I/GA II/EE [28] | ethylmalonic acid, glutaric acid, 3-hydroxy glutaric acid, 2-hydroxyglutaric acid |
LC-MS/MS | second | Primarily available through a contract with another laboratory |
| Tyrosinemia type I [29] | Succinylacetone | LC-MS/MS | second | Now included in the primary screening test of amino acids and acylcarnitines by FIA-MS/MS |
| Neuronal ceroid lipofuscinosis 2 [30] |
tripeptidyl protease 1 activity |
LC-MS/MS | first | 2/3 of Taiwan, ScreenPlus (pilot) |
| Wolman disease, cholesterol ester storage disease | lysosomal acid lipase activity |
LC-MS/MS | first | ScreenPlus (pilot) |
| Niemann-Pick C | bile acid B | LC-MS/MS | first | ScreenPlus (pilot) |
| α-Mannosidosis | α-mannosidosis activity | LC-MS/MS | first | ScreenPlus (pilot) |
| MLD | C16:0-sulfatide | LC-MS/MS | first | ArchimedLife, ScreenPlus (pilot) |
| MLD [31] | arylsulfatase A activity | LC-MS/MS | second | ScreenPlus (pilot) |
| CTX | cholestanetetrol glucuronide | LC-MS/MS or FIA-MS/MS |
first | ScreenPlus (pilot) uses LC-MS/MS; Amsterdam UMC (pilot) compares LC-MS/MS vs. FIA-MS/MS |
| CTX | 7-α-hydroxy-4-cholesten-3-one; 7-α,12 α-dihydroxycholest-4-en-3-one | LC-MS/MS | second | Primarily available through a contract with another laboratory |
1 Abbreviations: CTX, cerebrotendinous xanthomatosis; EE, ethylmalonic encephalopathy; GA I, glutaric acidemia type I; GA II, glutaric acidemia type II; MLD, metachromatic leukodystrophy; MPS, mucopolysaccharidosis; SCAD, short-chain acyl-CoA dehydrogenase deficiency; X-ALD, X-linked adrenoleukodystrophy.