Table 3 Outcomes for treated patients

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)

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 (1^st 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)

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

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)