Table 2.
Clinical, biochemical, and molecular findings in suspected VLCADD cases identified by NBS with one or no mutations in ACADVL
| DBS (NBS) (48 h) | Plasma (confirmatory test) | Mutations in ACADVL a | VLCAD activityb (LF) (%) | Therapy | Age/clinical outcomec | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C14:1 (μmol/L) | C14:1/C2 | C14:1/C16 | C14:1/C12:1 | C14:1 (μmol/L) | C14:1/C2 | C14:1/C16 | C14:1/C12:1 | ||||||
| NRd | <0.27–0.50 | <0.015–0.030 | <0.037–0.140 | <7–7.3 | <1 month | <0.17 | <0.023 | <1.27 | <5.69 | ||||
| ID | |||||||||||||
| P13 | 2.20 | 0.123 | 0.40 | 7.33 | 0.50 | 0.080 | 2.94 | 5.0 | c.990_994delCAAGC (p.Lys331Cysfs*26) (no del) | 25 | No | 4 years/Asymp | |
| P14e | 1.44 | 0.073 | 0.41 | 2.36 | 0.14 | 0.017 | 1.40 | 2.3 | c.199A>T (p.Lys67Ter) | NS | No | 12 months/Asymp | |
| P15 | 1.15 | 0.029 | 0.24 | 2.25 | 0.36 | 0.028 | 1.64 | 2.0 | c.896_898delAGA (p.Lys299del) | 57 | No | 21 months/Asymp | |
| P16 | 1.09 | 0.047 | 0.25 | 2.32 | 0.38 | 0.040 | 1.19 | 2.2 | c.1102_1103delCA (p.Gln368Valfs*26) (no del) | 20 | No | 4 years/Asymp | |
| P17 | 1.02 | 0.043 | 0.22 | 2.91 | 0.87 | 0.072 | 2.49 | 2.2 | c.294_297delGACA (p.Gln98Hisfs*18) | 18 | No | 3 years/Asymp | |
| P18f | 0.93 | 0.031 | 0.15 | 2.74 | 0.15 | 0.016 | 1.50 | 3.0 | c.896_898delAGA (p.Lys299del) | NS | No | 12 months/Asymp | |
| P19f | 0.87 | 0.033 | 0.21 | 2.72 | 0.13 | 0.014 | 1.18 | 3.3 | c.896_898delAGA (p.Lys299del) | NS | No | 12 months/Asymp | |
| P20 | 0.80 | 0.030 | 0.23 | 1.86 | 0.22 | 0.038 | 0.79 | 1.2 | c.896_898delAGA (p.Lys299del) | 33 | No | 2.5 years/Asymp | |
| P21 | 0.87 | 0.050 | 0.30 | 2.29 | 0.15 | 0.020 | 2.14 | 3.8 | c.515T>C (p.Leu172Pro) (no del) | NS | No | 4.5 years/Asymp | |
| P22 | 0.82 | 0.040 | 0.23 | 2.00 | 0.09 | 0.012 | 1.13 | 3.0 | c.643T>C (p.Cys215Arg) | NS | No | 17 months/Asymp | |
| P23 | 0.81 | 0.005 | 0.03 | 4.00 | 0.08 | 0.010 | 0.62 | 0.8 | c.1627T>C (p.Phe543Leu) | 34 | No | 2 years/Asymp | |
| P24 | 0.75 | 0.031 | 0.19 | 1.74 | 0.09 | 0.011 | 1.29 | 1.8 | c.481G>A (p.Ala161Thr) | NS | No | 14 months/Asymp | |
| P25 | 0.70 | 0.020 | 0.11 | 2.41 | 0.08 | 0.008 | 1.00 | 2.7 | c.694G>A (p.Ala232Thr) | NS | No | 14 months/Asymp | |
| P26 | 0.65 | 0.027 | 0.18 | 1.44 | 0.05 | 0.006 | 1.00 | 2.5 | c.1037C>T (p.Ala346Val) | NS | No | 20 months/Asymp | |
| P27 | 0.61 | 0.023 | 0.15 | 1.69 | 0.09 | 0.014 | 0.75 | 1.3 | c.1322G>C (p.Gly441Ala) | NS | No | 13 months/Asymp | |
| P28 | 0.46 | 0.02 | 0.14 | 1.39 | 0.20 | 0.010 | 0.87 | 1.3 | c.272C>T (p.Pro91Leu) | NS | No | 21 months/Asymp | |
| P29 | 0.61 | 0.027 | 0.17 | 1.56 | 0.06 | 0.008 | 0.35 | 2.0 | NS | 57 | No | 14 months/Asymp | |
| P30 | 0.61 | 0.012 | 0.10 | 1.97 | 0.02 | 0.004 | 0.22 | 1.0 | No mutations | NS | No | 2.5 years/Asymp | |
| P31 | 0.59 | 0.026 | 0.14 | 1.28 | 0.03 | 0.004 | 0.43 | 1.5 | No mutations | NS | No | 18 months/Asymp | |
| P32 | 0.56 | 0.018 | 0.16 | 1.27 | 0.04 | 0.004 | 0.31 | 1.3 | No mutations | NS | No | 2 years/Asymp | |
| P33e | 0.53 | 0.023 | 0.15 | 1.29 | 0.05 | 0.006 | 0.45 | 1.0 | No mutations | NS | No | 12 months/Asymp | |
| P34 | 0.52 | 0.023 | 0.14 | 1.33 | 0.02 | 0.003 | 0.40 | 1.0 | No mutations | NS | No | 14 months/Asymp | |
| P35 | 0.50 | 0.025 | 0.17 | 1.25 | 0.06 | 0.006 | 0.50 | 1.5 | No mutations | NS | No | 22 months/Asymp | |
| P36 | 0.44 | 0.024 | 0.11 | 1.22 | 0.05 | 0.008 | 0.83 | 1.3 | No mutations | NS | No | 18 months/Asymp | |
Cases are ordered by decreasing C14:1 levels in DBS and genotype found. Novel mutations are in bold
aMutations in ACADVL: no del no deletions
bVLCAD residual activity: % of intra-assay control; LF lymphocytes, NS not studied
cClinical outcome: Asymp asymptomatic (normal anthropometric parameters; normal neurologic and cardiologic examination)
d NR normal range
eFraternal twins
fIdentical twins