Table 2. IEMs Identified by Plasma Clinical Metabolomic Screening.

RUSP category and IEM No.	IEM name	OMIM No.a	Family No.	Key disease-related analytes detected in plasmab
Conditions not on RUSP
1	Adenylosuccinase deficiency (ADSLD)23	103050	28, 85, 390, 499, 584, 1749	N6-succinyladenosine
2	AICA-ribosiduria due to ATIC deficiency	608688	1797	N6-succinyladenosine
3	α-methylacyl-CoA racemase deficiency (AMACRD)c	614307	847	Phytanate, 7-α-hydroxy-3-oxo-4-cholestenoated
4	Aromatic L-amino acid decarboxylase deficiency (AADCD)18,24	608643	180, 812	3-Methoxytyrosine, 3-methoxytyramine sulfate ↓,d vanillylmandelate ↓, dopamine 3-O-sulfate ↓d
5	Autism, susceptibility to, X-linked 6 (AUTSX6)	300872	576, 814, 1461	N6,N6,N6-trimethyllysine, acetylcarnitine ↓, propionylcarnitine ↓, carnitine ↓, deoxycarnitine ↓
6	β-ureidopropionase deficiency (UPB1D)	613161	1258	3-Ureidopropionate, 5,6-dihydrothymine, 5,6-dihydrouracil, 3-aminoisobutyrate ↓
7	Brown-Vialetto-Van Laere syndrome 2 (BVVLS2)21	614707	1757	Riboflavin (due to initiation of supplement), pyridoxine and pyridoxate (normalized in response to riboflavin), medium chain (C6, C8, C10:1) and very long chain acylcarnitines (C24), 2-hydroxyglutarate, methylsuccinate, ethylmalonate, kynurenine,d N-formylanthranilic acid,d kynurenate ↓,d picolinate ↓,d methionine sulfone ↓d
8	Carbamoyl phosphate synthetase I deficiency, hyperammonemia due to	237300	184	Pyroglutamine,d citrulline ↓
9	Cerebral creatine deficiency syndrome 2 (CCDS2)	612736	57, 234, 347, 1550	Guanidinoacetate, creatine ↓
10	D-bifunctional protein deficiency33	261515	958, 1486	1-Lignoceroyl-GPC (24:0), docosadienoate, multiple sphingomyelins ↓, phosphatidylcholines ↓
11	Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta (DEE25)26	615905	39, 41, 52	Citrate
12	Dihydrolipoamide dehydrogenase deficiency (DLDD)	246900	137	Lactate, pyruvate, 3-methyl-2-oxobutyrate,d 3-methyl-2-oxovalerate,d 4-methyl-2-oxopentanoate,d 2-hydroxyglutarate
13	Encephalopathy, ethylmalonic (EE)25	602473	430, 1246, 1470, 1603	Ethylmalonate, butyrylcarnitine, isobutyrylcarnitine, isovalerylcarnitine, glutarylcarnitine, 2-methylbutyrylcarnitine, methylsuccinate, phenol sulfate ↓, 3-indoxyl sulfate ↓, glycolithocholate sulfate ↓
14	Epilepsy, pyridoxine-dependent (EPD)	266100	102, 933	Pipecolate, 6-oxopiperidine-2-carboxylate
15	Fructose intolerance, hereditary (HFI)	229600	902	Fructose
16	GABA-transaminase deficiency20	613163	27, 292, 387, 1333	2-Pyrrolidinone,d succinimide,d succinamic acidd
17	Glutaric aciduria III (GA3)	231690	207	Glutarate, arachidate (20:0),d octadecadienedioate (C18:2-DC),d hexadecanedioate,d octadecenedioate (C18:1-DC),d ximenoylcarnitine (C26:1)d
18	Glycerol kinase deficiency (GKD)27	307030	562, 987	Glycerol, long chain and very long chain monoacylglycerolsd
19	Glycine encephalopathy (GCE)	605899	514	Glycine
20	Glycogen storage disease 1A (GSD1A)	232200	1347	Lactate, urate, pyruvate, palmitoyl-linoleoyl-glycerol,d glucose ↓
21	Homocystinuria due to deficiency of n(5,10)-methylenetetrahydrofolate reductase activity	236250	156	Methionine sulfoxide ↓,d betaine ↓, methionine ↓, methionine sulfone ↓d
22	Homocystinuria-megaloblastic anemia, cblG complementation type (HMAG)	250940	923	S-adenosylhomocysteine,d methionine ↓
23	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHHS)	238970	557	Ornithine, homocitrulline, N-δ-acetylornithined
24	Isopentenyl-diphosphate delta isomerase 1 (IDI1)a	604055	1733	Deoxycholate,d 1-(1-enyl-stearoyl)-2-docosahexaenoyl-GPE (P-18:0/22:6),d octadecadienedioate (C18:2-DC),d dodecadienoate (12:2),d 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE (P-16:0/18:2),d 1-(1-enyl-stearoyl)-2-linoleoyl-GPE (P-18:0/18:2),d 1,2-dilinoleoyl-GPC (18:2/18:2),d multiple sphingomyelins ↓
25	L-2-hydroxyglutaric aciduria (L2HGA)	236792	469	2-Hydroxyglutaric acid
26	Lesch-Nyhan syndrome (LNS)	300322	358	Inosine, uracil
27	Lipoyltransferase 1 deficiency (LIPT1D)28	616299	731	Leucine, isoleucine, valine, 2-hydroxyadipate, isovalerylcarnitine, glycine isovalerylglycine, isovalerylcarnitine (C5), 1-stearoyl-2-arachidonoyl-GPI (18:0/20:4), 3-hydroxy-3-methylglutarate, 2-aminoadipate, tyrosine, arginine, serine oxalate (ethanedioate) ↓, malonate ↓
28	Liver failure, infantile, transient (LFIT)	613070	595	3-(4-Hydroxyphenyl) lactate,d phenyllactate,d 4-hydroxyphenylpyruvate,d N-acetylphenylalanine,d fumarate,d alanine,d lactate, pyruvate, glycochenodeoxycholate,d glycohycholate,d taurocholate,d bilirubin
29	Lysinuric protein intolerance (LPI)	222700	1302	Ornithine ↓, urea ↓, arginine ↓, lysine ↓, dimethylarginine ↓d
30	Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 (MC5DN2)	614052	34, 1556	3-Methylglutaconate, 3-methylglutarylcarnitine, alanine, lactate
31	Mitochondrial DNA depletion syndrome 1 (mitochondrial neurogastrointestinal encephalomyopathy type) (MTDPS1)29	603041	1120	Thymidine, thymine, 5,6-dihydrothymine ↓
32	Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) (MTDPS9)	245400	50	Succinylcarnitine, propionylcarnitine, methylmalonate, hexanoylcarnitine, butyrylcarnitine, malate ↓
33	Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D)30	616277	1261	β-hydroxyisovalerate, 1-lignoceroyl-GPC (24:0),d 3-hydroxy-3-methylglutarate, laurate (12:0)d
34	Multiple mitochondrial dysfunctions syndrome 1 (MMDS1)31	605711	1469	Glycinee
35	Neurodegeneration, infantile-onset, biotin-responsive (NERIB)	618973	171	Pantothenate (vitamin B5) ↓,d carnitine ↓,d multiple carnitine derivatives ↓d
36	Ornithine transcarbamylase deficiency, hyperammonemia due to32	311250	177, 819, 1094	Orotate, ornithine, N-carbamoylaspartate,d uridine, uracil, alanine, aspartate, glutamine, citrulline ↓, arginine ↓
37	Peroxisome biogenesis disorder 1A (Zellweger) (PDB1A)33	214100	361	Pipecolate, docosadioate,d multiple sphingomyelins ↓
38	Peroxisome biogenesis disorder 4A (Zellweger) (PDB4A)	614862	440	Pipecolate, 1-lignoceryl-GPC,d 7-HOCA,d hexadecanedioate,d octadecanedioate,d eicosanodioate,d docosadioate,d phytanate, multiple sphingomyelins ↓,d plasmalogens ↓, phosphatidylcholines ↓,d phosphatidylethanolamines ↓d
39	Peroxisome biogenesis disorder 8A (Zellweger) (PDB8A)	614876	252	Pipecolate, phytanate, long chain fatty acids, 1-lignoceryl-GPC,d 7-HOCA,d hexadecanedioate,d octadecanedioate,d eicosanodioate,d docosadioate,d phytanate, multiple sphingomyelins ↓,d plasmalogens ↓, phosphatidylcholines ↓,d phosphatidylethanolamines ↓d
40	Phosphoglycerate dehydrogenase deficiency (PSATD)19	610992	1253	Serine ↓, glycine ↓, glycerophosphocholine ↓,d glycerophosphoethanolamine ↓,d multiple lipids ↓d
41	Phosphoserine aminotransferase deficiency (PHGDHD)19	601815	863, 1063	Serine ↓, glycine ↓, glycerophosphocholine ↓,d glycerophosphoethanolamine ↓,d multiple lipids ↓d
42	Pyruvate dehydrogenase, α-1 (PDHA1)	300502	393	Lactate, pyruvate, alanine
43	Short stature, developmental delay, and congenital heart defects (SDDHD; TKT)34	617044	1034	Ribitol, arabitol/xylitol, ribonate, erythronate, arabonate/xylonate,d erythritol, ribose
44	Smith-Lemli-Opitz syndrome (SLOS)	270400	373, 647	7-Dehydrocholesterol, cholesterol ↓
45	Spastic paraplegia 9B, autosomal recessive (SPG9B)	616586	60, 1449	Proline ↓, ornithine ↓, citrulline ↓
46	Spondyloepimetaphyseal dysplasia, Genevieve type (SEMDG)	610442	1483	N-acetylglucosamine/N-acetylgalactosamine,d N-acetylneuraminate ↓
47	Succinic semialdehyde dehydrogenase deficiency (SSADHD)	271980	721	2-Pyrrolidinone,d 4-guanidinobutanoated
48	Transaldolase deficiency (TALDOD)34	606003	420, 1028	Ribitol, ribonate, erythronate, arabitol/xylitol, erythritol, sedoheptulose
49	Urocanase deficiency (UROCD)35	276880	606, 1411	Trans-urocanate, imidazole propionate,d cis-urocanate
RUSP core conditions
50	Acyl-CoA dehydrogenase, medium-chain, deficiency of (ACADMD)	201450	226, 1441, 1602, 1800	Hexanoylcarnitine, octanoylcarnitine, hexanoylglycine, cis-4-decenoylcarnitine
51	Adrenoleukodystrophy (ALD)	300100	341	Numerous significant abnormalities in bile acid, fatty acid, and lipid metabolism
52	Carnitine deficiency, systemic primary (CDSP)	212140	704, 1222	Carnitine ↓, multiple acylcarnitines ↓
53	Citrullinemia, classic32	215700	1006	Citrulline, N-acetylcitrullined
54	Galactosemia I (GALAC1)	230400	1489, 1519	Galactitol, galactonate
55	Glutaric acidemia I (GA1)	231670	916, 1091	Glutarylcarnitine, glutarate
56	HSD10 mitochondrial disease (HSD10MD)	300438	854, 1072, 1450	Tiglylcarnitine, tiglylglycine (rare), 2-hydroxy-3-methylvalerate, β-hydroxyisovalerate, isoleucine, 3-hydroxyisobutyrate, 3-hydroxy-2-ethylpropionate,d 2-methylbutyroylcarnitined
57	Isovaleric acidemia (IVA)	243500	1035	Isovalerylcarnitine, 2-methylbutyroylcarnitine, isovalerylglycine, isovalerate
58	Maple syrup urine disease (MSUD)	248600	86, 1648	Leucine, valine, isoleucine, allo-isoleucine, 2-hydroxy-3-methylvalerate, 3-methyl-2-oxovalerate, isovalerate, β-hydroxyisovalerate, N-acetylisoleucine,d N-acetylleucine,d 3-methyl-2-oxobutyrated
59	Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	251000	62, 792, 971, 1121, 1178	Propionylcarnitine, 2-methylcitrate, methylmalonate
60	Phenylketonuria (PKU)	261600	482, 672, 1191, 1299	Phenylalanine, phenylpyruvate, phenyllactate, phenylacetate, N-acetylphenylalanine,d N-formylphenylalanine,d 3-(4-hydroxyphenyl) lactated
61	Propionic acidemia	606054	51, 127, 223, 1223	Propionylcarnitine, propionylglycine, 2-methylcitrate, glycine
62	Tyrosinemia, type I (TYRSN1)	276700	791	3-(4-Hydroxyphenyl) lactate,d 4-hydroxyphenylpyruvate, phenyllactate, tyrosine, N-acetyltyrosine
RUSP secondary conditions
63	2-Methylbutyryl-CoA dehydrogenase deficiency	610006	1274	2-Methylbutyroylcarnitine, 2-methylbutyrylglycine, 3-hydroxy-2-ethylpropionate, tiglylcarnitine, isobutyrylglycine
64	3-Hydroxyisobutyryl-CoA hydrolase deficiency (HIBCHD)	250620	70	3-Hydroxyisobutyrate ↓
65	Acyl-CoA dehydrogenase, short-chain, deficiency of (ACADSD)	201470	253, 833	Ethylmalonate, butyrylcarnitine, methylsuccinate
66	Argininemia32	207800	33, 254, 539, 650, 829, 1683	Arginine, argininate, N-acetylarginine, 2-oxoarginine, dimethylarginine, 4-guanidinobutanoate, homoarginine, orotate, uracil, urea ↓, ornithine ↓
67	Citrullinemia, type II, neonatal onset	605814	1753	Citrulline, homocitrulline,d arginine, argininate,d homoarginine,d methionine, phenyllactate, 4-hydroxyphenylpyruvate, N-acetylphenylalanine,d argininosuccinate, bilirubin, galactonate, galactitol, cholesterol
68	Hyperphenylalaninemia, nonphenylketonuria mild, included	261600	201	Phenylalanine, phenylpyruvate, phenyllactate
69	Methylmalonic aciduria and homocystinuria, cblC type (MAHCC)	277400	315	Methylmalonate, 3-hydroxy-3-methylglutaric acid, propionylcarnitine, methionine ↓
70	Multiple acyl-CoA dehydrogenase deficiency (MADD)	231680	522, 1156, 1532	α-hydroxyisovalerate,d 2-hydroxy-3-methylvalerate, 2-hydroxyglutarate, 2-methylbutyrylglycine, glutarate, glutarylcarnitine, ethylmalonate, methylsuccinate,d butyrylcarnitine and a wide variety of various acylcarnitines

Abbreviations: ↓, Decrease in analyte; IEMs, inborn errors of metabolism; OMIM, Online Mendelian Inheritance in Man; RUSP, Recommended Uniform Screening Panel.

^aMendelian Inheritance in Man numbers are shown for all disorders except isopentenyl-diphosphate-δ-isomerase 1 deficiency, for which the Mendelian Inheritance in Man gene number is provided (https://www.omim.org).

^bAnalytes listed achieved a z score less than or equal to −2 or greater than or equal to 2 compared with reference control population or were identified as a rare molecule and were not z scored. All analytes listed represent elevations unless indicated with a downward arrow (↓).

^cPristanate was not identified in this patient sample because of the absence of pristanate in the compound library at the early time of testing; the current platform identifies this metabolite as a rare compound.

^dIndicates analytes that were not previously reported for the indicated IEMs and may represent new biomarkers.

^eElevated glycine and lactate were found in cerebrospinal fluid metabolomics.