Background
Methods
Study population
Patient (metabolic center)
|
Gender
|
Current age (y)
|
Age at diagnosis
|
NBS+
|
Decompensation at diagnosis.
|
Pregnancy
|
Birth mode
|
GA
|
---|---|---|---|---|---|---|---|---|
Patients born before introduction of LCHADD into NBS program, diagnosed clinically
| ||||||||
1 (Munich)
| M | 15.3 | 5 m | no* | yes | HELLP | CS | 37 weeks |
2 (Innsbruck)
| M | 14.1 | 23 m | no* | yes | normal | CS | 38 weeks |
3 (Graz)
| F | 12.2 | 3 m | no* | yes | normal | vaginal | Term |
Patients born after introduction of LCHADD into NBS program (group 1-3):
| ||||||||
Group 1: patients showing symptoms before NBS results were available:
| ||||||||
4 (Innsbruck)
| F | 7.8 | 15 d | yes | (yes) | IUD | CS | 32 weeks |
5 (Vienna)
| M | 7.3 | 15 d | yes | (yes) | normal | vaginal | 35 weeks |
6 (Innsbruck)
| M | 2.7 | 15 d | yes | (yes) | IUD | CS | 32 weeks#
|
Group 2: patients with false negative NBS results:
| ||||||||
7 (Graz)
| M | 10.6 | 4 m | no** | yes | HELLP | CS | 31 weeks#
|
8 (Salzburg)
| M | 5.2 | 5 m | no** | yes | HELPP | CS | 29 weeks#
|
Group 3: patients with positive NBS results, asymptomatic:
| ||||||||
9 (Vienna)
| F | 10.8 | 1 d | Yes | no | normal | vaginal | Term |
10 (Vienna)
| F | 9.5 | 6 d | Yes | no | twin pregnancy | CS | 29 weeks#
|
11 (Graz)
| F | 3.7 | 1 d | yes | no | HELLP | CS | 32 weeks#
|
12 (Vienna)
| M | 2.8 | 10 d | Yes | no | preeclampsia | CS | 34 weeks |
13 (Vienna)
| F | 2.7 | 1 d | Yes | no | path. CTG | CS | 25 weeks#
|
14 (Vienna)
| M | 0.9 | 2 d | Yes | no | normal | vaginal | 40 weeks |
Summary for the 14 LCHADD patients:
| ||||||||
8 M/6 F | median: 7.6 y | median:15 d | NBS + 9/14 | 8/14 | 4/14 HELLP | CS 10/14 | 9/14 preterm 64%; 6/9 IRDS | |
range: 0.9-15.3 | range: 1d-20 m | 64% | 57% | 1/14 preecl. | 71% |
Data collection
Statistics
Results
Diagnosis and onset of symptoms
Clinical signs – short- and long-term organ involvement
Patient
|
Current age (y)
|
Hepatopathy
|
CMP
|
Retinopathy
|
NG/PEG
|
Late night feeds
|
---|---|---|---|---|---|---|
Patients born before introduction of LCHADD into NBS program, diagnosed clinically
| ||||||
1
| 15.3 | 156 m | 108 m | PEG 24 m | X* | |
2
| 14.1 | 23 m | 23 m | 23 m | X | |
3
| 12.2 | 3 m | 3 m | 24 m | ||
Patients born after introduction of LCHADD into NBS program (group 1-3):
| ||||||
Group 1: patients showing symptoms before NBS results were available:
| ||||||
4
| 7.8 | |||||
5
| 7.3 | 39 m | ||||
6
| 2.7 | 9 m | ||||
Group 2: patients with false negative NBS results:
| ||||||
7
| 10.6 | 4 m | 4 m | 42 m | ||
8
| 5.2 | 5 m | 5 m | 38 m | PEG 12 m | X* |
Group 3: patients with positive NBS results, asymptomatic:
| ||||||
9
| 10.8 | 50 m | ||||
10
| 9.5 | 4 m | 56 m | PEG 11 m | X | |
11
| 3.7 | NG 7 m | ||||
12
| 2.8 | X | ||||
13
| 2.7 | neonatally | X | |||
14
| 0.9 | X | ||||
Summary for the 14 LCHADD patients:
| ||||||
36% | 50% | 57% | 29% | 50% |
Creatine kinase
Patient
|
n CK
|
max CK (in U/l)
|
max CK (age)
|
n CK >1,000 (in U/l)
|
---|---|---|---|---|
1
| 57 | 40,381 | 16.2 y | 19 |
2
| 127 | 34,160 | 4.2 y | 31 |
3
| 36 | 39,501 | 5.8 y | 10 |
4
| 132 | 10,170 | 1.9 y | 19 |
5
| 67 | 8,876 | 3.9 y | 17 |
6
| 15 | 299 | 0.8 y | 0 |
7
| 52 | 62,216 | 2.7 y | 6 |
8
| 69 | 73,260 | 0.9 y | 27 |
9
| 22 | 95,000 | 2.7 y | 8 |
10
| 71 | 67,500 | 2.6 y | 14 |
11
| 29 | 68,600 | 0.6 y | 6 |
12
| 26 | 12,000 | 2.1 y | 8 |
13
| 9 | 449 | 1.7 y | 0 |
14
| 10 | 725 | 2 d | 0 |
Median
| 44 | 40,381 | 2.35 y | 14 |
Total carnitine and acyl carnitine profiles
Acylcarnitine profile at diagnosis
|
Acylcarnitine profile at last follow-up
| |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Patient
|
Age at diagn.
|
TC
|
C0
|
C16OH
|
C18:1OH
|
C18OH
|
Age at last follow-up
|
TC
|
C0
|
C16OH
|
C18:1OH
|
C18OH
|
1 | 5 m | - | 5 | 0.57 | 1.19 | 0.39 | 15.0 y | - | 39 | 0.19 | 0.22 | - |
2 | 23 m | 21 | 3 | 0.17 | 0.08 | - | 13.5 y | 18 | 11 | 0.16 | 0.17 | 0.23 |
3 | 3 m | - | 11 | 0.69 | 0.54 | - | 9.0 y | 32 | 25 | 0.01 | 0.05 | 0.10 |
4 | *15 d | 45 | 27 | 0.30 | 0.50 | 0.20 | 7.2 y | 14 | 9 | 0.37 | 0.44 | 1.00 |
5 | 15 d | 42 | 20 | 0.20 | 0.16 | 0.40 | 6.8 y | 18 | 10 | 0.11 | 0.49 | 0.54 |
6 | *15 d | 91 | 45 | 0.48 | 0.62 | 0.50 | 2.1 y | 15 | 7 | 0.42 | 0.66 | 0.78 |
7 | 4 m | 10 | 5 | 0.24 | 0.66 | - | 9.0 y | 45 | 37 | - | 0.01 | 0.01 |
8 | 5 m | 17 | 9 | 0.98 | 0.74 | - | 3.6 y | 48 | 28 | 0.25 | 0.11 | 0.24 |
9 | 1 d | 13 | 8 | 0.82 | - | 0.49 | 8.6 y | 11 | 6 | 0.31 | 0.65 | 0.41 |
10 | 6 d | 118 | 97 | 0.35 | - | 0.80 | 8.7 y | 17 | 10 | 0.12 | 0.10 | 0.20 |
11 | 1 d | 77 | 33 | - | - | - | 3.2 y | 61 | 46 | 0.13 | - | - |
12 | *10 d | 103 | 56 | 0.25 | 0.37 | 0.34 | 2.2 y | - | - | 0.31 | 0.42 | 0.35 |
13 | 1 d | 39 | 18 | 0.21 | 0.27 | 0.30 | 2.1 y | 20 | 10 | 0.52 | 0.69 | 0.95 |
14 | 2 d | 68 | 32 | 1.1 | 0.41 | 0.69 | 0.3 y | 22 | 10 | 0.53 | 0.40 | 0.47 |
Median | 15 d | 44 | 19 | 0.35 | 0.50 | 0.40 | 7.0 | 19 | 10 | 0.25 | 0.40 | 0.30 |
Range | 1d-20 m | 10-118 | 3-97 | 0.17-1.1 | 0.08-1.19 | 0.2-0.8 | 0.3-15.0 | 11-61 | 6-46 | 0.01-0.53 | 0.01-0.69 | 0.01-1.0 |
PEG/NG tube feeding/late evening feeds/bolus before sports/concomitant medication
Hospitalizations
Patient
|
1st hospitalization and time of LCHADD diagnosis (age)
|
Length of 1st hospitalization (days)
|
Number of hospitalizations including 1st hospitalization
|
Length of hospitalizations (total days)
|
Range (days)
|
Median (days)
|
---|---|---|---|---|---|---|
1
| 5 months | 16 | 8 | 79 | 1-23 | 7 |
2
| 23 months | 26 | 18 | 76 | 1-26 | 2 |
3
| 3 months | 22 | 7 | 48 | 2-22 | 3.5 |
4
| GA 32 weeks | 29 | 34 | 114 | 1-29 | 3 |
5
| GA 35 weeks positive family history | 17 | 77 | 1-10 | 3 | |
6
| GA 32 weeks | 36 | 6 | 16 | 2-36 | 3 |
7
| GA 31 weeks; Dg. LCHADD 4 months | 46 | 17 | 168 | 2-46 | 4 |
8
| GA 29 weeks | 26 | 22 | 181 | 2-29 | 4 |
9
| NBS | 6 | 22 | 1-9 | 4 | |
10
| GA 29 weeks | 89 | 23 | 247 | 1-89 | 8 |
11
| GA 32 weeks | 55 | 10 | 94 | 1-55 | 3 |
12
| GA 34 weeks | 23 | 6 | 27 | 3-23 | 4 |
13
| GA 25 weeks | 91 | 2 | 94 | 3-91 | 47 |
14
| NBS positive family history | 6 | 2 | 23 | 6-17 | 11.5 |
Median
| 27.5 | 9 | 78 | |||
Range
| 6 – 91 | 2 – 34 | 16 – 247 |
Patient
|
Y1
|
Y2
|
Y3
|
Y4
|
Y5
|
Y6
|
Y7
|
Y8
|
Y9
|
Y10
|
Y11
|
Y12
|
Y13
|
Y14
|
Y15
|
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1
| 39/2 | 1/1 | 3/1 | 19/1 | 11/2 | 6/1 | |||||||||
2
| 0/0 | 26/1 | 13/4 | 14/3 | 20/7 | 3/2 | 0 | 0 | 0 | 0 | 1/1 | 0 | 0 | 0 | |
3
| 33/3 | 5/2 | 4/1 | 3/1 | 3/1 | ||||||||||
4
| 45/7 | 26/6 | 18/3 | 21/7 | 4/2 | 10/3 | 13/4 | 6/2 | |||||||
5
| 11/3 | 18/5 | 2/1 | 13/2 | 5/1 | 6/2 | 22/3 | ||||||||
6
| 50/5 | 2/1 | |||||||||||||
7
| 109/5 | 22/4 | 2/1 | 12/3 | 3/1 | 20/3 | |||||||||
8
| 94/8 | 59/8 | 20/5 | 5/2 | 3/1 | ||||||||||
9
| 4/1 | 5/1 | 9/1 | 0 | 0 | 5/2 | 0 | 0 | 0 | 4/1 | |||||
10
| 176/13 | 48/4 | 14/3 | 4/1 | 0 | 0 | 0 | 5/2 | 0 | ||||||
11
| 84/6 | 1/1 | 3/1 | 6/2 | |||||||||||
12
| 0 | 10/2 | 17/4 | ||||||||||||
13
| 91/1 | 0 | 3/1 | ||||||||||||
14
| 23/2 |
Long-term management - diet
Heptanoate (C7)
Patient
|
Age at evaluation
|
Body weight (kg)
|
Total fat intake
|
% MCT of fat in diet
|
Walnut oil (in ml and g/kg/d)
|
Heptanoate (C7) (in ml and g/kg/d)
|
C7 since
|
DHA suppl.
|
kcal/d
|
---|---|---|---|---|---|---|---|---|---|
1
| 15.0 y | 72,6 | 30% | 20% | 0 ml | - | +267 mg | 3000 | |
2
| 13.5 y | 55.5 | 40% | 50% | 5 ml = 0.10 | 30 ml = 0.60 | 9.4 y | - | 1800 |
3
| 10.0 y | 29.7 | 33.5% | 72% | 10 ml = 0.34 | - | +89 mg | 1700 | |
4
| 7.2 y | 24.9 | 25% | 52% | 10 ml = 0.40 | 20 ml = 0.80 | 7 y | - | 1738 |
5
| 7.3 y | 29.0 | 27% | 56% | 3 ml = 0.10 | - | *200 mg | 1653 | |
6
| 2.7 y | 13.3 | 36% | 47% | 6 ml = 0.45 | 10 ml = 0.75 | 13 m | - | 953 |
7
| 10.6 y | 36.9 | 29% | 69% | 10 ml = 0.27 | - | +89 mg | 1900 | |
8 #
| 4.0 y | 17.4 | 15% | 80% | 10 ml = 0.57 | 10 ml = 0.60 | 13 m | - | 1452 |
9
| 10.7 y | 25.0 | 21% | 68% | 2 ml = 0.08 | - | *200 mg | 1850 | |
10
| 9.3 y | 25.1 | 28% | 70% | 13 ml = 0.52 | - | *100 mg | 1782 | |
11
| 3.7 y | 15.4 | 25% | 64% | 13 ml = 0.84 | - | +89 mg | 1300 | |
12
| 2.8 y | 15.3 | 30% | 63% | 4 ml = 0.26 | - | *100 mg | 1377 | |
13
| 2.7 y | 11.1 | 30% | 61% | 3 ml = 0.27 | - | *150 mg | 1166 | |
14
| 0.9 y | 8.62 | 33% | 65% | 3 ml = 0.35 | - | *150 mg | 862 | |
Median | 5.6 y | 28.5% | 62% | 0.34 | |||||
Range | 0.9 – 15.0 | 15 – 40 | 20 – 80 | 0.08 – 0.84 |