Table 4.
diagnostic biomarkers for PA and MMA that are not significantly altered during AMD
| Analyte | Matrix | PROPIONIC ACIDURIA | METHYLMALONIC ACIDURIA | ||||
|---|---|---|---|---|---|---|---|
| No AMD | AMD | P-value | No AMD | AMD | P-value | ||
| Median + SD [Min-Max] (N) | Median + SD [Min-Max] (N) | Median + SD [Min-Max] (N) | Median + SD [Min-Max] (N) | ||||
| Targeted metabolic assays | |||||||
| Propionylcarnitine | Plasma | 54.4 + 19.6 [23.0–99.5] (34) | 49.7 + 25.6 [24.0–128.0] (23) | NS | 21.0 + 21.7 [2.7–83.7] (68) | 78.0 + 81.0 [14.8–175.5] (3) | NS |
| Glycine | Plasma | 1381 + 362 [350–1962] (73) | 1160 + 514 [265–2051] (35) | NS | 492 + 369 [168–1916] (77) | 334 + 152 [226–441] (2) | NS |
| Methylcitric acid | Plasma | 49.5 + 14.8 [24.9–78.9] (12) | NS | 2.2 + 2.8 [1.0–10.9] (11) | NS | ||
| Methylcitric acid | Urine | 697 + 383 [425–968] (3) | NS | NS | |||
| 3-Hydroxy-propionic acid | Urine | 232 + 99 [89–349] (10) | 738 + 355 [184–1534] (13) | NS | 13.0 + 18.6 [0. – 86.0] (57) | 9.5 + 76.8 [4.0–161.0] (4) | NS |
| Methylmalonylcarnitine | Plasma | 7.6 + 7.7 [3.4–20.2] (5) | NS | ||||
| Methylmalonic acid | Plasma | 74 + 346 [3–1327] (52) | NS | ||||
| Methylmalonic acid | Urine | 727 + 4651 [64–21,587] (174) | 4062 + 3200 [536–9044] (7) | NS | |||
| Acetylcarnitine | Plasma | 10.1 + 7.5 [1.6–42.2] (34) | 10.9 + 9.5 [1.3–43.9] (23) | NS | 9.2 + 5.8 [2.1–29.9] (68) | 12.6 + 24.4 [3.9–49.9] (3) | NS |
| Untargeted DI-HRMS | |||||||
| Propionylcarnitine | Plasma | 12.0 + 80.8 [− 2.8–363] (23) | 272 + 193 [1.5–730] (15) | NS | 37.9 + 171 [− 1.4–684] (61) | 596 + 835 [5.7–1186] (2) | NS |
| Glycine | Plasma | 9.5 + 4.8 [− 2.4–18.5] (23) | 4.9 + 4.1 [− 0.4–14.7 (15) | NS | 1.8 + 2.2 [− 1.1–8.5] (61) | 2.7 + 3.0 [0.5–4.8] (2) | NS |
| 2-Methylcitric acid (3 isomers) | Plasma | 57.4 + 43.1 [− 1.8–147] (23) | 93.7 + 31.4 [30.4–139] (15) | NS | 9.0 + 9.5 [− 0.6–41.3] (61) | 41.1 + 27.0 [22.1–60.2] (2) | NS |
| Propionylglycine (9 isomers) | Plasma | 28.5 + 29.3 [− 3.0–91.1] (23) | 80.6 + 50.1 [4.0–177.1] (15) | NS | 1.6 + 3.1 [− 2.3–10.4] (61) | 5.8 + 5.3 [2.0–9.6] (2) | NS |
| Methylmalonic acid (3 isomers) | Plasma | 25.3 + 77.5 [− 0.0–376] (61) | 150 + 175 [26.3–274] (2) | NS | |||
| Methylmalonylcarnitine | Plasma | 2.4 + 9.1 [− 2.3–29.7] (61) | 22.9 + 31.7 [0.4–45.3] (2) | NS | |||
Results of targeted metabolic assays in plasma are presented in μmol/L, results of targeted metabolic assays in urine are presented in mmol/mol creatinine. All p-values were adjusted according to the Bonferroni method. A p-value < 0.05 was considered statistically significant. Abbreviations DI-HRMS direct-infusion high-resolution mass spectrometry, Max maximum value, Min minimum value, (N) number of samples, NS not significant, P p-value, SD standard deviation