Table 1.
Serum amino acid concentrations (mean ± standard deviation, μmol/L) in patients attending the National Alkaptonuria Centre over a 36-month period
| Amino acid (reference range, μmol/L) | Baseline (n = 50) | 3 months (n = 37) | 6 months (n = 29) | 12 months (n = 37) | 24 months (n = 34) | 36 months (n = 20) |
|---|---|---|---|---|---|---|
| Phenylalanine (30–76)E,a | 87.42 (13.9) | 84.4 (18.3) | 91.5 (22.5) | 94.5 (13.5) | 92.9 (13.6) | 97.6 (15.0) |
| Tyrosine (29–92)a | 69.8 (15.7) | 670.7 (155.0) | 666.4 (162.3) | 692.9 (119.8) | 649.4 (183.6) | 724.8 (116.8) |
| Tryptophan (40–79)E,a | 51.8 (11.5) | 50.9 (9.9) | 48.5 (11.9) | 48.1 (11.1) | 51.1 (10.2) | 53.5 (14.7) |
| Glutamine (326–800)b | 571.2 (108.0) | 476.2 (79.4) | 495.1 (81.1) | 527.6 (86.0) | 525.4 (77.8) | 469.4 (103.5) |
| Asparagine (30–70)b | 72.1 (15.1) | 64.7 (14.6) | 65.3 (17.9) | 69.2 (11.0) | 61.3 (11.8) | 61.4 (9.1) |
| Aspartic acid (2–5)c | 39.8 (9.7) | 38.2 (10.9) | 37.9 (9.9) | 38.1 (6.7) | 39.5 (8.7) | 45.4 (17.0) |
| Glutamic acid (26–151)c | 128.9 (40.4) | 129.2 (56.6) | 141.1 (63.5) | 151.8 (37.4) | 137.5 (32.4) | 149.5 (49.2) |
| Cystine (36–61)d | 11.1 (9.3) | 6.9 (4.6) | 8.3 (8.4) | 9.6 (9.1) | 13.9 (9.1) | 15.7 (13.5) |
| Methionine (10–41)E,d | 25.5 (6.6) | 21.8 (4.5) | 23.7 (5.9) | 25.8 (5.4) | 24.4 (4.3) | 25.2 (5.3) |
| Glycine (120–436)e | 316.7 (77.6) | 299.5 (60.6) | 330.5 (61.6) | 343.2 (63.2) | 329.9 (75.1) | 332.6 (74.4) |
| Isoleucine (20–91)E,e | 69.7 (17.6) | 63.2 (15.5) | 64.5 (15.7) | 64.8 (12.1) | 66.6 (13.5) | 72.5 (18.0) |
| Leucine (44–169)E,e | 148.8 (27.8) | 132.1 (28.4) | 137.1 (30.7) | 139.4 (21.6) | 139.7 (20.7) | 134.6 (33.1) |
| Proline (66–330)e | 204.3 (89.6) | 183.3 (76.3) | 207.9 (108.9) | 180.4 (63.5) | 182.3 (53.3) | 182.5 (75.8) |
| Valine (79–313)E,e | 240.4 (43.4) | 222.9 (44.6) | 226.7 (45.4) | 234.2 (36.0) | 241.9 (40.2) | 250.3 (52.7) |
| Alanine (112–529)e | 462.0 (96.9) | 444.8 (92.0) | 485.1 (124.8) | 427.8 (83.3) | 448.5 (82.6) | 450.6 (79.5) |
| Histidine (43–111)E,f | 84.1 (12.3) | 85.0 (12.8) | 86.7 (16.5) | 80.7 (9.5) | 85.2 (11.7) | 79.3 (10.0) |
| Lysine (66–242)E,f | 191.3 (32.2) | 180.5 (33.8) | 180.45 (38.8) | 177.8 (27.9) | 183.8 (28.0) | 185.6 (27.4) |
| Arginine (14–102)f | 105.2 (23.4) | 113.9 (31.1) | 116.2 (26.9) | 98.1 (13.8) | 96.6 (15.9) | 108.2 (18.0) |
| Serine (69–206)g | 162.3 (28.7) | 149.8 (21.9) | 155.5 (29.6) | 161.3 (18.6) | 157.9 (30.5) | 162.4 (25.6) |
| Threonine (43–218)E,g | 132.2 (27.5) | 114.5 (25.5) | 112.7 (27.0) | 112.5 (21.3) | 113.4 (23.6) | 124.5 (27.8) |
| Phenylalanine/tyrosine (0.80–1.0) | 1.28 (0.21) | 0.13 (0.04) | 0.13 (0.03) | 0.14 (0.03) | 0.16 (0.1) | 0.13 (0.04) |
| Tyrosine/LNAA (0.0–0.14) | 0.10 (0.01) | 0.55 (0.07) | 0.54 (0.10) | 0.54 (0.05) | 0.52 (0.09) | 0.54 (0.06) |
| Phenylalanine/LNAA (0.09–0.13) | 0.13 (0.01) | 0.07 (0.01) | 0.07 (0.02) | 0.07 (0.01) | 0.08 (0.02) | 0.07 (0.01) |
| Arginine/BCAA (0.16–0.23) | 0.23 (0.05) | 0.27 (0.07) | 0.27 (0.07) | 0.23 (0.04) | 0.22 (0.05) | 0.24 (0.04) |
| BCAA/AAA (Fisher’s ratio) (2.7–3.5) | 2.93 (0.37) | 0.56 (0.14) | 0.71 (0.86) | 0.56 (0.09) | 0.71 (0.49) | 0.56 (0.13) |
All samples were collected in a fasted state (overnight fast >8 h). Baseline refers to pre-nitisinone therapy; at 3 months, patients received 2 mg nitisinone every other day; after 3 months, patients received 2 mg nitisinone daily. EssentialE amino acids. Amino acid reference ranges were determined in-house. Amino acid ratio reference ranges were adopted from (Antener et al. 1981; Lieberman 1999; Kouchiwa et al. 2012). LNAA large neutral amino acids, BCAA branched chain amino acids, AAA aromatic amino acid
aAromatic
bAmidic
cAcidic
dSulphur containing
eAliphatic
fBasic
gHydroxylic