Table 2 Clinical, biochemical, neuroradiological, and genetic features of patients with loss-of-function mutations in NDUFAF2
Patient # | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Reference | Ogilivie et al. [5] | Barguthi et al. [6] | Barguthi et al. [6] | Hoefs et al. [8] | Janssen et al. [9] | Herzer et al. [7] | Calvo et al. ([6] | Calvo et al. [16] | Calvo et al. [16] | Ghaloul Gonzalez et al. [10] | Current study (P1) | Current study (P2) | Current study (P3) | Current study (P4) |
Gender | F | F | M | M | F | M | NA | Na | Na | M | F | F | F | F |
IUGR | NA | NA | NA | NA | Yes | NA | NA | Na | Na | NA | Yes | Yes | Yes | Yes |
Consanguinity | No | Yes | Yes | Yes | Yes | No | NA | Na | NA | NA | Yes | Yes | Yes | Yes |
Age at presentation (first symptom) | 12 m (N/ & ataxia) | 20 m (apnea) | 8 m (HY, DD, N, OA) | 5d (HCM) | Birth (severe GR) | 14 mo (N/DD) | NA | NA | NA | Infancy (N, DD, HY, DD) | 6 mo (N) | 9 mo (N,S) | 5 mo (S,GR) | 5 mo (S,N) |
Age at death | 13y | 2y | 21 mo | 11 mo | 14 m | 27 mo | NA | NA | NA | 19 mo | 3.5y | 19 mo | 15mo | Alive at 5y |
Optic atrophy (age at onset) | 3 y | NA | 8 mo | 6 mo | NA | 26 mo | NA | NA | NA | NA | 18 mo | No | NA | 3y |
Nystagmus (age at onset) | 12 mo | 20 mo | 8 mo | NA | NA | 14 mo | NA | NA | NA | Yes | 6 mo | 9 mo | NA | 5 mo |
Strabismus (age at onset) | NA | 20 mo | NA | NA | NA | NA | NA | NA | NA | NA | 18 mo | 9 mo | 5 mo | 5 mo |
GR (age at onset) | 3y | No | NA | NA | Birth | NA | NA | NA | Na | Yes | birth | 10 mo | 5 mo | 3 mo |
DD (age at onset) | 3y | No | 8 mo | Birth | Birth | NA | NA | NA | NA | Yes | 6 mo | 10 mo | 9 mo | 7 mo |
Apnea (age at onset) | 8y | 20 m | 18 mo | 8 mo | NA | 26 m | NA | NA | NA | 15 mo | 18 mo | 10 mo | 15 mo | 12 mo |
Gastrostomy (age) | 8y | No | 18 m | NA | NA | NA | NA | NA | NA | No | 2y | No | No | 20 mo |
Mechanical ventilation (age) | 8y | No | 18 m | 8 mo | NA | 26 mo | NA | NA | NA | 15 mo | 3y | 18 m | No | 26 mo |
Beginning to sit (age) | Age appropriate | Yes | No | No | No | yes | NA | NA | NA | NA | 16 mo | 12 mo | 12 mo | 11 m |
Beginning to walk (age) | Age appropriate | Yes | No | No | No | 22 m | NA | NA | NA | No | 2y | No | No | No |
Initial words (age) | Age appropriate | Yes | No | No | No | NA | NA | NA | NA | NA | 18 m | No | No | No |
Ser Lactate | N | Normal | Normal | NA | ↑ | ↑ | NA | NA | NA | ↑ | Normal | ↑ | ND | ↑ |
Csf Lactate | ↑ | Normal | Normal | NA | NA | ↑ | NA | NA | NA | NA | NA | ↑ | ND | Na |
Complex I activity in tissue % of normal (tissue) | 20% (muscle) | 36% (fibroblast | 24% (fibroblast | 36% (Fibroblast) 20% (muscle) | 45% (fibroblast | 12% (muscle) 59% (fibroblast | NA | NA | NA | NA | 42% (fibroblast | ND | ND | ND |
NDUFAF2 mutation | c.182C > T (hom) p.R45X | c.1A > T (hom) p.M1L | c.1A > T (hom) p.M1L | c.114C > G (hom) p.Y38X | Triple gene deletion including NDUFAF2 (hom) | c.9G > A (p.W3X) (hom) | C.221G > A (p.W74*) (hom) | C.103delA (p.I35Sfsx17) (hom) | C.103delA (p.I35Sfsx17) (hom) | NDUFAF2 gene deletion (hom) | NDUFAF2 intragenic deletion (hom) | NDUFAF2 intragenic deletion (hom) | ND | NDUFAF2 intragenic deletion (hom) |
Brain MRI (age) | Normal (12mo) abnormal signal: BS,T, CS (3.5y) Generalized atrophy (10y) | Abnormal signal BS, CE (20 mo) | Abnormal signal BS, CE (19 mo) | Cer atrophy, CC hypoplasia (4 mo) | NA | Abnormal signal BS, CS (27 mo) | NA | NA | NA | Abnormal signal BS, CE, CS, BG (15mo) | Abnormal signal BS (18 mo) Abnormal signal BS, T, CS (18 mo) | ND | ND | Normal (6 mo) Abnormal signal BS, T,CS,CE, BG (16 mo) |