Table 1. Clinical features of eight ACAD9 patients.
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | |
|---|---|---|---|---|---|---|---|---|
| Clinical features | ||||||||
| Gender | M | F | F | M | F | M | F | F |
| Affected relatives | One brothera (H6) | − | 1a in utero 1 brothera at birth (CH) | 1 sistera at birth | 1 sistera (5 mo) | − | − | − |
| Age at first symptoms | Neonatal | Neonatal | 12 m | 18 m | 9 y | 4 m | 15 m | 12 m |
| Current age | aH11 | a71 d | a6 y | 15 y | 35 y | 22 y | a21 m | a18 m |
| Early cardiac symptoms | ||||||||
| Cardiac hypertrophy | + | + | + | + | + | + | + | + |
| Heart transplantation | − | − | 2 y | 9 y | 18 y | − | − | − |
| Delayed neurological symptoms | ||||||||
| Cognitive impairment | nr | nr | + | + | − | − | − | − |
| Seizures | nr | nr | − | + | − | − | − | − |
| Brain MRI | nd | leucodystrophy | nd | nd | N at 14 y | nd | N | − |
| Other organ involvement | − | Liver failure | Exercise intolerance | Tubulopathy Exercise intolerance | Tubulopathy, POF | Optic atrophy | − | − |
| Laboratory | ||||||||
| Plasma lactate (mmol/l) | 20 | >3 | 7,4 | 6,4 | 4 | >3 | 8 | 5,5–14 |
| Complex I deficiency | ||||||||
| Heart | N | Severe | Mild | Severe | Mild | Severe | Severe | |
| Muscle | Severe | Severe | Mild | Severe | Severe | N | Severe | |
| Fibroblasts | Mild | N | N | N | N | N | nd | Mild |
| Nucleotide change | c.1249C>Tc.1030–1G>T | c.2T>Gc.1015T >G | c.358delTc.1594C>T | c.976G>Cc.1595G>A | c.151-2A>Gc.1298G>A | c.1237G>Ac.1552C>T | c.1552C>Tc.1564-6_1569del | c.1 A >Gc.796C>T |
| Aminoacid change | p.(Arg417Cys)acceptor splice site | p.(Met1?)p.(Phe339Val) | p.(Phe120Serfs*9)p.(Arg532Trp) | p.(Ala326Pro)p.(Arg532Gln) | acceptor splice sitep.(Arg433Gln) | p.(Glu413Lys)p.(Arg518Cys) | p.(Arg518Cys)splice site | p.(Met1?)p.(Arg266Trp) |
Abbreviations: CH, cardiac hypertrophy; d, day; NA, not applicable; nr, not relevant; N, normal; nd, not done; m, month; POF: premature ovarian failure; w, week, y, year.
a
Deceased. ACAD9 reference sequence is NM_014049.4.