Table 1.
Potential impact of metabolite instability on the interpretation of carnitine and acylcarnitine concentrations.
| Parameter | Disorder | Retrospective Analysis of IEMs | Validation Studies for NBS Programs |
|---|---|---|---|
| Risk Category | Potential Effect on Cutoff Target | ||
| C0 (low) | CUD | False-negative | Too high |
| C0 (high) | CPT-I | False-positive | Too high |
| C2 (low) | CUD, CPT-II | False-positive | Too low |
| C3 (low) | CUD | False-positive | Too low |
| C3 (high) | PROP, MUT, Cbl A-D | False-negative | Too low |
| C4 | SCAD, EE, IBG, FIGLU a, MADD | False-negative | Too low |
| C5 | IVA, MADD, 2MBG, EE | False-negative | Too low |
| C6 | MCAD, MADD | False-negative | Too low |
| C8 | MCAD, MADD | False-negative | Too low |
| C10:1 | MCAD | False-negative | Too low |
| C10 | MADD, MCAD | False-negative | Too low |
| C12:1 | MADD, VLCAD | False-negative | Too low |
| C12 | MADD, CPT-II, CACT, VLCAD | False-negative | Too low |
| C14:1 | VLCAD, MADD, LCHAD/TFP | False-negative | Too low |
| C14 | MADD, CPT-II, VLCAD, CACT, LCHAD/TFP | False-negative | Too low |
| C16:1 | VLCAD, LCHAD/TFP, CACT, CPT-II | False-negative | Too low |
| C16 (low) | CPT-I, CUD | False-positive | Too low |
| C16 (high) | CACT, CPT-II | False-negative | Too low |
| C18:2 (low) | CPT-I | False-positive | Too low |
| C18:2 (high) | CPT-II, CACT | False-negative | Too low |
| C18:1 (low) | CPT-I, CUD | False-positive | Too low |
| C18:1 (high) | CPT-II, CACT | False-negative | Too low |
| C18 (low) | CPT-I, CUD | False-positive | Too low |
| C18 (high) | CPT-II, CACT | False-negative | Too low |
| C5OH + C4DC | 3MCC, HMG, MCD, 3MGA, BTD, BKT, 2M3HBA | False-negative | Too low |
| C18:1OH | LCHAD/TFP | False-negative | Too low |
| C16DC | PBD | False-negative | Too low |
The potential consequences associated with (1) the interpretation of retrospectively analysed carnitine and acylcarnitine concentrations in DBS upon long-term storage at room temperature for the detection of IEMs, and (2) using control DBS stored at room temperature for validation studies on cut-off targets for NBS programs. a FIGLU is only associated with a high C4-carnitine when butylation is applied. Abbreviations (in alphabetical order): 2M3HBA, 2-methyl-3-hydroxybutyric aciduria (i.e., alpha-methylacetoacetic aciduria; online mendelian inheritance in man (OMIM) #203750); 2MBG, 2-short/branched chain acyl-CoA dehydrogenase deficiency (# 610006); 3MCC, 3-methylcrotonyl-CoA carboxylase deficiency (#210200, #210210); 3MGA, 3-methylglutaconic aciduria (#250950, #302060); BKT, beta-ketothiolase deficiency (#203750); BTD, biotinidase deficiency (#253260); CACT, carnitine-acylcarnitine translocase deficiency (#212138); Cbl, cobalamin deficiency (complementation group); CPT-I, carnitine palmitoyltransferase I deficiency (#255120); CPT-II, carnitine palmitoyltransferase II deficiency (#255110); CUD, carnitine uptake defect (#212140); EE, ethylmalonic encephalopathy (#602473); FIGLU, formiminoglutamic aciduria (#229100); IBG, isobutyryl-CoA dehydrogenase deficiency (#611283); IVA, isovaleryl-CoA dehydrogenase deficiency (#243500); HMG, 3-hydroxy-3-methylglutaric aciduria (#246450); LCHAD, long-chain L-3-Hydroxy dehydrogenase deficiency (#609016); MADD, multiple acyl-CoA dehydrogenase deficiency (#231680); MCAD, medium-chain acyl-CoA dehydrogenase deficiency (#607008); MCD, holocarboxylase synthetase deficiency (#253270); MUT, methylmalonic aciduria (#251000, 251100, 251110); PBD, peroxisome biogenesis disorder (complementation group); PROP, propionic aciduria (#606054); SCAD, short-chain acyl-CoA dehydrogenase deficiency (#201470); TFP, trifunctional protein deficiency (#609015); VLCAD, very long-chain acyl-CoA dehydrogenase deficiency (#201475).