Table 2.
Clinical, biochemical and molecular genetic features of AsymX patients are summarized in Table 2
| Patient #/study ID/sex/diagnosis/age of diagnosis/current age | Presenting symptom (age of onset)/other clinical features | Initial investigations AC1,2,3/TC1,2,3/FC1,2,3/UOA/TRR% | Molecular genetic investigations | Outcome |
|---|---|---|---|---|
| 1/2/M/CPT-I deficiency/neonatal/3yrs | No | N/NP/75.4/↑3-HIVA /NP | HMZ c.1436C > T (p.Pro479Leu) in CPTIA | Normal |
| 2/5/F/CPT-I deficiency/6yrs/26yrs | No | NP | HMZ c.1436C > T (p.Pro479Leu) in CPTIA | Normal |
| 3/8/M/CPT-I deficiency/45yrs/53yrs | No | NP | HMZ c.1436C > T (p.Pro479Leu) in CPTIA | Normal |
| 4/9/F/CPT-I deficiency/neonatal/6yrs | No | N/N/117.75/NP/NP | HMZ c.1436C > T (p.Pro479Leu) in CPTIA | Normal echo (4yrs) |
| 5/11/F/CPT-I deficiency/39yrs/48yrs | No | NP | HMZ c.1436C > T (p.Pro479Leu) in CPTIA | Normal |
| 6/12/F/CPT-I deficiency/neonatal/2yrs | No | N/66.9/51.3/N/NP | HMZ c.1436C > T (p.Pro479Leu) in CPTIA | atrial septal aneurysm, PFO, ASD, PDA (1mo) |
| 7/50/F/CPT-I deficiency/2yrs/3yrs | No | NP | HMZ c.1436C > T (p.Pro479Leu) in CPTIA | Normal |
| 8/51/M/CPT-I deficiency/neonatal/5yrs | No | NP | HMZ c.1436C > T (p.Pro479Leu) in CPTIA | Normal |
| 9/18/M/CTD deficiency/neonatal/7yrs | No | NP/NP/NP/NP/NP | HMZ c.769C > T (p.Arg257Trp) in SLC22A5 | Normal echo (5yrs) |
| 10/19/F/CTD deficiency/32yrs/37yrs | No | NP/2.2/1.7/N/90.88 | HMZ c.845G > A (p.Arg282Gln) in SLC22A5 | Normal |
| 11/24/M/CTD deficiency/neonatal/3yrs | No | N/6.4/4.2/N/NP | HMZ c.845G > A (p.Arg282Gln) in SLC22A5 | Hospital admissions (n = 2), normal echo (2yrs) |
| 12/25/M/CTD deficiency/neonatal/3mo | No | NP/6.1/4.8/N/NP | HMZ c.845G > A (p.Arg282Gln) in SLC22A5 | Normal |
| 13/22/F/CTD deficiency/38yrs/44yrs | No/ fatigue (retrospectively at the time of diagnosis) | NP/ < 2/ < 2/NP/NP | HMZ c.248G > T (p.Arg83Leu) in SLC22A5 | Normal echo (42yrs) |
| 14/23/F/CTD deficiency/28yrs/40yrs | No/ fatigue (retrospectively at the time of diagnosis) | NP/ < 2/ < 2/NP/NP | NP | Normal echo (30yrs) |
| 15/28/M/CTD deficiency/neonatal/6yrs | No | N/10.6/8.4/NP/NP | CMP HTZ c.1463G > A (p.Arg488His)/c.424G > T (p.Ala142Ser)/c.136C > T (p.Pro46Ser) in SLC22A5 | Normal echo (5yrs) |
| 16/32/F/CTD deficiency/26yrs/33yrs | No/ fatigue (retrospectively at the time of diagnosis) | NP/10.1/5.1/N/NP |
CMP HTZ c.364G > T (p.Asp122Tyr)/ c.505C > T (p.Arg169Trp) in SLC22A5 |
Normal echo (27yrs) |
| 17/36/M/CTD deficiency/neonatal/9yrs | No/ myalgia (8yrs) | NP/NP/NP/NP/NP |
CMP HTZ c.424G > T (p.Ala142Ser) /c.1463G > A (p.Arg488His) /c.1324GC_1325AT (p.Ala442Ile) in SLC22A5 |
Normal echo (6yrs) |
| 18/38/M/LCHAD deficiency/neonatal/6yrs | No/ RM (2yrs), retinopathy, myopathy (6 yrs) |
C16OH = 0.73, C18OH = 0.87, C18:1OH = 0.54/N/N/N/NP |
HMZ c.1528G > C (p.Glu474Gln) in HADHA | Hospital admissions (n = 6), normal echo (6yrs) |
| 19/39/F/LCHAD deficiency/neonatal/3yrs | No/RM, myopathy |
C16OH = 1.05, C18OH = 0.91, C18:1OH = 1.1/N/NP/NP/NP |
HMZc.1528G > C (p.Glu474Gln) in HADHA | Hospital admissions (n = 4), normal echo (3yrs) |
| 20/53/M/LCHAD deficiency/neonatal/7mo | Hypoglycemia (neonatal, but diagnosed prenatally) | C16:1OH = 0.33, C16OH = 0.78, C18:1OH = 0.45, C18OH = 0.40/N/N/N/NP | HMZ c.1528G > C (p.Glu474Gln) in HADHA | Hospital admissions (n = 2), normal echo (12yrs) |
| 21/40/F/VLCAD deficiency/neonatal/7yrs | No/ RM, myopathy (3 yrs) | C14:1 = 0.13, C14:2 = 0.06/N/N/NP/NP | CMP HTZ c.1375dupC (p. p.Arg459ProfsX4)/c.1700G > A (p.Arg567Gln) in ACADVL | Hospital admissions (n = 1), dilated ascending aorta in echo (6yrs) |
| 22/43/F/VLCAD deficiency/neonatal/12yrs | No/RM, myalgia (12 yrs) | N/N/N/↑AA, SUA, SEA/NP |
CMP HTZ c.848 T > C (p.Val283Ala)/ c.1375dupC (p.Arg459ProfsX4) in ACADVL |
Hospital admissions (n = 1) |
| 23/44/F/VLCAD deficiency/neonatal/9yrs | No/ myalgia (4yrs) | N/N/N/NP/NP |
CMP HTZ c.779C > T (p.Thr260Met/ c.1733 T > C (p.Met578Thr) in ACADVL |
Hospital admissions (n = 3), normal echo (7yrs) |
| 24/46/F/CACT deficiency/4yrs/8yrs | No |
C16 = 0.85, C18:1 = 0.83, C18:2 = 0.25/N/ 14.9/NP/NP |
CMP HTZ c.897dupC (p.Asn300Glnfs*24)/c.269 T > G (p.Phe90Cys) in SLC25A20 | PDA in echo (6mo) |
Reference Ranges: Free carnitine1 7.3–30.4; Free carnitine2 18.6–55.0; Free carnitine3 25.3–57.0; Total carnitine1 14.0–47.0; Total carnitine2 24.9–72.1; Total carnitine3 32.5–73.6; C161 0.04–0.41; C162 0.03–0.22; C163 0.03–0.19; C16-DC1 < 0.06; C16-DC2 < 0.03; C16-DC3 0.03–0.09; C16-OH1 < 0.05; C16-OH2 < 0.04; C16-OH3 < 0.02; C18:11 0.04–0.20; C18:12 0.03–0.23; C18:13 0.03–0.26; C18:21 < 0.10; C18:22 < 0.12; C18:23 < 0.13; C18-OH1 < 0.03; C18-OH2 < 0.03; C18-OH3 < 0.02; C18:1OH1 < 0.02; C18:1OH2 < 0.03; C18:1OH3 < 0.02; C16:1OH1 < 0.27; C16:1OH2 < 0.11; C16:1OH3 < 0.03; C14:11 < 0.26; C14:12 < 0.28; C14:13 < 0.11; C14:21 < 0.10; C14:22 < 0.13; C14:23 < 0.11
1 Indicates reference range for age group newborn-2 months
2 Indicates reference ranges for age group 2 months-6 years
3 Indicates reference ranges for age group 18 years and up
3-HIVA 3-OH-isovaleric acid; AA adipic acid; AC acylcarnitines; ASD atrial septal defect; CACT carnitine acylcarnitine translocase; Car carnitine; CPT-I carnitine palmitoyltransferase I; CPT-II carnitine palmitoyltransferase II; CMP HTZ compound heterozygous; CTD carnitine transporter defect; Echo echocardiography; FC free carnitine; F female; HMZ homozygous; LCHAD long-chain 3-hydroxyacyl-CoA dehydrogenase; MAD multiple acyl-CoA dehydrogenase; mo months; NB newborn; N normal; NP not performed; NR not reported; PDA patent ductus arteriosus; PFO patent foramen ovale; RM rhabdomyolysis; SEA sebacic acid; SUA suberic acid; TRR tubular reabsorption rate; UOA urine organic acids; yrs year(s); VLCAD very long-chain acyl-CoA dehydrogenase