Table 3.
Outcomes for treated patients
| Patient # | Diet | Time period | Met μM | MRI | Clinical | |
|---|---|---|---|---|---|---|
| Start years | End years | Mean ± SD (N) | ||||
| Patients without evidence of CNS problems who had periods of dietary methionine restriction | ||||||
| 3 | Normal | Birth | 4.5 m | 2262 ± 350 (3) | ||
| Restricted | 4.5 m | 3.4 y | 462 ± 70 (5) | |||
| Normal | 3.4 y | 21.5 y | 777 ± 169 (8) | Normal (6 y) | Normal (21.5 y) | |
| 17 | Normal | Birth | 0.8 m | 648 (1) | ||
| Restricted | 0.8 m | 21.4 y | 282 ± 42 (3) | |||
| Normal | 21.4 y | 22 y | 314 (1) | n.d. | Normal (21.4 y) | |
| 18 | Normal | Birth | 1 m | 305 (1) | ||
| Restricted | 1 m | 14 y | 135 ± 40 (3) | |||
| Normal | 14 y | 21.2 y | 327 ± 241 (2) | n.d. | Normal (21.2 y) | |
| 19 | Normal | Birth | 1 m | 622 (1) | ||
| Restricted | 1 m | 16.4 y | 156 ± 36 (5) | |||
| Normal | 16.4 y | 16.5 y | 175 (1) | n.d. | Normal (16.5 y) | |
| 21 | Normal | Birth | 0.4 m | 596 (1) | ||
| Restricted | 0.4 m | 5.8 y | 282 ± 95 (6) | |||
| Normal | 5.8 y | 7.1 y | 436 ± 1 (2) | n.d. | Normal (7.1 y) | |
| 48 | Normal | Birth | 1 m | 643 ± 646 (3) | ||
| Restricted | 1 m | 5.4 y | 545 ± 118 (50) | n.d. | Normal (5.4 y) | |
| 53 | Normal | Birth | 4.3 m | 303 ± 257 (2) | ||
| Normal | 5.2 m | 1.2 y | 495 ± 275 (4) | |||
| Restricted | 1.2 y | 2.3 y | 266 ± 96 (3) | n.d. | Normal (2.3 y) | |
| 58 | Birth | 1 m | 783 ± 337 (3) | |||
| Restricted | 1 m | 6 m | 134–268 (2) | |||
| Normal | 6 m | 6.5 m | 536 (1) | |||
| Restricted | 6.5 m | 6 y | 67–268 (2) | |||
| Normal | 6 y | 36 y | 263 ± 83 (7) | n.d. | No problems (6 y) | |
| Patients with evidence of CNS problems who had periods of dietary methionine restriction | ||||||
| 1 | Normal | Birth | 2 m | 954 ± 401 (2) | ||
| Restricted | 2 m | 24 y | 100–600 (2) | Abnormal (20.7 y) | Normal intelligence (24 y) | |
| 5 | Normal | Birth | 3 m | 1345 ± 661 (5) | ||
| Restricted | 6 m | 2.5 y | 899 ± 129 (4) | Considered slow | ||
| Normal | 2.5 y | 26.1 y | 909 ± 272 (3) | Normal (13 y) | Wechsler Intelligence Scale verbal 88, performance 84 (7.5 y) | |
| 9 | Normal | Birth | 1 m | 1217 ± 354 (2) | ||
| Restricted | 1 m | 1.2 y | 220 ± 176 (10) | |||
| Normal | 1.2 y | 8.7 y | 879 ± 140 (5) | Normal (6 y) | IQ 65 (1st percentile) (6 y) | |
| 13 | Normal | Birth | 1.3 m | 697 ± 87 (2) | ||
| Restricted | 1.7 m | 10 m | 193 ± 83 (4) | |||
| Normal | 10 m | 10 y | 485 ± 49 (4) | Abnormal (8 y) | Slow at school (16 y) | |
| 20 | Normal | Birth | 1.5 m | 1528 ± 85 (4) | Abnormal (0.1 y) | |
| Restricted | 1.5 m | 6.6 y | 684 ± 234 (14) | Normal (4.9 y) | Normal (5.4 y) | |
| Normal | 6.6 y | 10.5 y | 1298 ± 112 (5) | Abnormal (10 y) | ||
| Restricted | 10.5 y | 10.8 y | 1180 (1) | |||
| 30 | Normal | Birth | 0.6 m | 740 | ||
| Restricted + betaine | 0.6 m | 2.5 y | 400–1580 | |||
| Restricted + betaine + B6 | 2.5 y | 3.9 y | 1080–1370 | Abnormal (3.8 y) | IQ 121 (3.5 y) | |
| Normal | 3.9 y | 9 y | 1050 | Improved (5 y) better (7 y) | ||
| 31 | Normal | Birth | 3 m | |||
| Restricted | 3 m | 1.8 y | Abnormal (0.8y) | Development normal | ||
| Abnormal (3 y) | ||||||
| 32 | Normal | Birth | NA | 1805 ± 92 (2) | ||
| Restricted | NA | 5.2 Y | 740–1150 | Abnormal (5 Y) | ||
| Normal | 5.2 Y | 9.4 Y | NA | Abnormal (9.4 y) | IQ 108 (9.4 y); neurologically normal | |
| 43 | Normal | Birth | 4 m | 949 ± 691 (2) | ||
| Normal | 4 m | 6 m | 1145 | |||
| Restricted | 9.6 m | 3.2 y | 928 ± 74 (8) | |||
| Normal | 3.2 y | 3.8 y | 1120 (1) | Abnormal (3.8 y) | Performance IQ 78; reasoning 57 (3.3 y) | |
| Restricted | 4 y | 4.2 y | 994 (1) | |||
| 46 | Normal | Birth | 1.5 m | 1027 ± 542 (3) | ||
| Restricted | 1.5 m | 4 y | 332 ± 341 (28) | |||
| Normal | 4 y | 34 y | 1326 ± 159 (29) | Abnormal (30 y) | Physical and mental development normal (34 y) | |
| 61 | Normal | Birth | 735 | Normal | ||
| Restricted + betaine | 2 w | 3.59 y | 700–1100 | Abnormal (3.5 and 4.5 y) | Normal | |
| 62 | Normal | Birth | < 5 m | 461 (1) | ||
| Normal | 1 y | 2.1 y | 860 ± 424 (3) | Developmental delay; autistic action (2.2 y) | ||
| Restricted | 2.1 y | 2.4 y | 7 (1) | Normal (2.3 y) | Improved (2.4 y) | |
| Normal | 2.4 y | 4.3 y | 741 ± 71 (2) | IQ = 108 (3.3 y) | ||
| Normal (4.3 y) | ||||||
| 63 | Normal | Birth | 1 m | 1105 ± 235 (2) | ||
| Restricted | 1 m | 1 y | 570 (1) | Abnormal (0.8 y) | ||
| Normal | 1 y | 2.9 y | 905 ± 99 (3) | Worse (1.5 y) | No neurological signs (2.9 y) | |
| Patients treated with AdoMet supplementation only | ||||||
| 4 | Normal | Birth | 11 y | 600–1400 (2) | Abnormal (11 y) | Headaches, nystagmus, dysdiadochokinesis, increased tendon reflexes (11 y) |
| AdoMet, 400 mg bid | 11 y | 12 y | Normal (12 y) | |||
| AdoMet, 200 mg bid | 17 y | 32 y | 565 ± 139 (17) | Normal baby daughter (30 y) | ||
| 22 | Normal | Birth | 4.7 y | 1005–1676 (2) | Abnormal (4.7 y) | IQ 49 (3.7 y) |
| AdoMet, 400–800 mg bid | 4.7 | 7.4 y | 1528 (1) | Normal (6.4 y) | IQ improved to 69 (5.4y); awake EEG markedly improved (6.3 y); IQ 64 (7.4 y) | |
| 35 | Normal | Birth | 3 m | 1620 ± 107 (2) | ||
| ? | 3 m | 1.2 y | 1159 (1) | Abnormal (1.2 y) | ||
| AdoMet 100–200 mg bid | 1.3 y | 1.8 y | 759 ± 278 (2) | Improved overall (1.8 y) | ||
| 50 | Normal | Birth | <4.3 y | 878 ± 136 (3) | Abnormal (4.3 y) | |
| AdoMet, 200 mg bid | 4.4 y | 4.5 y | ||||
| AdoMet, 400 mg bid | 4.5 y | 4.9 y | Behavior considerably improved | |||
| 51 | Normal | Birth | 3.3 y | 641 ± 74 (2) | Abnormal | |
| AdoMet, 400 mg bid | 4.7 y | Not available | ||||
| Patients who had periods of dietary restriction and AdoMet supplementation | ||||||
| 7 | Normal | Birth | 0.5 m | 1445 ± 310 (2) | ||
| Restricted | 1 m | 4 m | 516 ± 192 (5) | |||
| Normal | 4 m | 6 m | 1138 (1) | |||
| Restricted | 6 m | 9 m | 1451 (1) | Normal (9 m) | Developmental delays | |
| Normal | 9 m | 14 y | 1457 ± 322 (10) | Abnormal (4.2 y) | Impaired function; fine tremor | |
| AdoMet, 200 mg/d | 14.1 y | Brief trial of AdoMet . Attempts to assess efficacy failed due to loss of follow-up. The supplement was stopped by the family who considered there had not been noticeable clinical improvement. | ||||
| 34 | Normal | Birth | 5.5 m | |||
| Restricted + AdoMet | 5.5 m | 8.3m | Improved clinically on combined methionine restriction and AdoMet supplemenation, but details not available. | |||
| 41 | Normal | Birth | 0.2 y | 919 ± 795 (4) | ||
| Restricted | 0.2 y | 6.7 y | 313 ± 226 (9) | Abnormal (0.2 y) | ||
| Restricted + AdoMet | 6.7 y | 7.6 y | 455 ± 104 (5) | Normal (7.1 y) | Appetite improved (7.1 y) | |
| 45 | Normal | Birth | 1.8 m | 760 ± 357 (2) | ||
| Normal | 1.8 m | 4.1 y | 901 ± 163 (4) | Abnormal (4 y) | Physical and neurologic examinations normal (4 y) | |
| Restricted + AdoMet | 4.1 | 4.7 | 468 ± 120 (4) | Improved (4.5 y) | ||
*Diet classified as methionine restriction only if continued for > 0.4 years and decreased plasma methionine by > 90 μM
w = weeks
m = months
y = years