Introduction
Patients and methods
Patients
Measurements
Statistical analysis
Results
Overview
Mutation | Complex I–IV activity (enzyme assay) | Total | |
---|---|---|---|
Decreased | Not decreased | ||
nDNA | 19 | 4 | 23 |
mtDNA | 22 | 8 | 30 |
None confirmed | 34 | 19 | 53 |
Total | 75 | 31 | 106 |
Clinical presentation
Defect and mut | Mut only | Defect only | No defect, no validated mut | Total | |
---|---|---|---|---|---|
Number of patients | 41 | 12 | 34 | 19 | 106 |
Leigh-like | 6 | 4 | 10 | 4 | 24 |
Livinga
| 71% (20/28) | 78% (7/9) | 62% (16/26) | 83% (10/12) | 71% (53/75) |
Age of living patientsa [median (range)] | 9 (3–17) years | 8 (3–15) years | 9.5 (3–38) years | 8.5 (6–20) years | 8 (3–38) years |
Age at onset [median (range)] | 10.5 months (0 months–8 years) | 9 months (0 months–5 years) | 5.5 months (0 months–6 years) | 10 months (0 months–2 years) | 9 months (0 months–8 years) |
Neonatal onset | 2 (5%) | 2 (17%) | 7 (21%) | 1 (5%) | 12 (11%) |
Seizure | 20% | 33% | 41% | 42% | 32% |
Involuntary movement | 10% | 25% | 18% | 16% | 15% |
Hypotonia | 24% | 42% | 9% | 32% | 23% |
Nystagmus/ ophthalmoplegia | 17% | 33% | 26% | 11% | 21% |
Dysphagia | 10% | 17% | 29% | 32% | 21% |
Respiratory distress | 24% | 17% | 41% | 37% | 31% |
Serum L/P (mean ± SD) (number of data available) | 26.4 ± 16.4 (36) | 22.9 ± 14.9 (10) | 21.4 ± 9.9 (27) | 18.2 ± 5.7 (16) | 23.0 ± 13.2 (89) |
CSF L/P (mean ± SD) (number of data available) | 27.2 ± 28.0 (30) | 20.7 ± 4.5 (9) | 25.0 ± 9.6 (20) | 18.7 ± 7.1 (14) | 24.1 ± 18.9 (73) |
Enzyme assay
Oxygen consumption rate
Patient | Enzyme analysis | MRR (%) |
---|---|---|
Pt139 | ns (Fb) | 136 |
Pt156 | ns (Fb) |
69
|
Pt161 | ns (Fb) |
36
|
Pt207 | ns (M, Fb) | 90 |
Pt216 | ns (M, Fb) | 94 |
Pt394 | ns (Fb) | 94 |
Pt430 | ns (M, Fb) |
62
|
Pt536 | ns (M, Fb) | 96 |
Pt545 | ns (M, Fb) |
53
|
Pt668 | ns (M, Fb) |
62
|
Pt696 | ns (Fb) | 127 |
Pt701 | ns (Fb) |
61
|
Pt703 | ns (M, Fb) | 81 |
Pt794 | ns (Fb) |
48
|
Pt822 | ns (M, Fb) | 108 |
Pt840 | ns (Fb) |
43
|
Pt1038 | ns (Fb) |
51
|
Pt1065 | ns (M, Fb) | 78 |
Pt1120 | ns (Fb) |
51
|
mtDNA analysis
Patient | Gene | Mutation | LS/LL | Enzyme assay | Heteroplasmy rate (%) | Tissue |
---|---|---|---|---|---|---|
Pt27 |
SURF1 (NM_003172.2) | c.743C>A:p.A248D | LS | CIV | ||
c.743C>A:p.A248D | ||||||
Pt756 |
SURF1 (NM_003172.2) | c.367_368del:p.R123Gfs | LS | CIV | ||
c.54+1G>T | ||||||
Pt981 |
SURF1 (NM_003172.2) | c.743C>A:p.A248D | LL | CIV | ||
c.54+1G>T | ||||||
Pt1066 |
SURF1 (NM_003172.2) | c.367_368del:p.R123Gfs | LS | CIV | ||
c.867G>A:p.W289X | ||||||
Pt1143 |
SURF1 (NM_003172.2) | c.743C>A:p.A248D | LS | CIV | ||
c.826_827ins18:p.V276_T277ins6 | ||||||
Pt312a
|
NDUFA1 (NM_004541) | c.55C>T:p.P19S | LS | CI | ||
Pt286 |
BOLA3 (NM_212552) | c.287A>G:p.H96R | LS | CC (I, II) | ||
c.287A>G:p.H96R | ||||||
Pt376 |
ECHS1 (NM_004092) | c.98T>C:p.F33S | LS | CIV | ||
c.176A>G:p.N59S | ||||||
Pt536 |
ECHS1 (ENST00000368547) | c.5C>T:p.A2V | LS | ns | ||
c.1A>G:p.M1V | ||||||
Pt1038 |
ECHS1 (NM_004092) | c.5C>T:p.A2V | LS | ns | ||
c.176A>G:p.N59S | ||||||
Pt1135 |
ECHS1 (NM_004092) | c.5C>T:p.A2V | LS | CI | ||
c.176A>G:p.N59S | ||||||
Pt101 |
NDUFAF6 (NM_152416) | c.371T>C:p.I124T | LS | CI | ||
c.805C>G:p.H269D | ||||||
Pt330 |
NDUFAF6 (NM_152416) | c.820A>G:p.R274G | LS | CI | ||
c.820A>G:p.R274G | ||||||
Pt512 |
NDUFAF6 (NM_152416) | c.226T>C:p.S76P | LS | CI | ||
c.805C>G:p.H269D | ||||||
Pt598 |
NDUFAF6 (NM_152416) | c.206A>T:p.D69V | LL | CI | ||
c.371T>C:p.I124T | ||||||
Pt866 |
NDUFAF6 (NM_152416) | c.371T>C:p.1124T | LS | CI | ||
c.805C>G:p.H269D | ||||||
Pt711 |
NDUFS4 (NM_002495) | c.340T>C:p.W114R | LS | CI | ||
c.340T>C:p.W114R | ||||||
Pt1087 |
NDUFS6 (NM_004553) | c.309+5G>A | LS | CC (I, IV) | ||
c.343T>C:p.C115R | ||||||
Pt1177 |
NDUFV2 (NM_021074) | c.427C>T:p.R143X | LS | CI | ||
c.580G>A:p.E194K | ||||||
Pt628 |
SCO2 (NM_001169109) | c.577G>A:p.G193S | LS | CC (I, IV) | ||
c.773T>C:p.M258T | ||||||
Pt751 |
GTPBP3 (NM_032620) | c.8G>T:p.R3L | LS | CC (I, IV) | ||
c.923_947del:p.E309Rfs | ||||||
Pt156 |
SLC19A3 (NM_025243) | c.372C>G:p.Y124X | LS | ns | ||
c.265A>C:p.S89R | ||||||
Pt416 |
MT-ND1
| m.3697G>A:p.G131S | LS | CI | 100 | F |
Pt619 |
MT-ND1
| m.3946G>A:p.E214K | LS | CC (I, IV) | 66 | M |
Pt179 |
MT-ATP6
| m.8993T>G:pL156R | LL | ns | nearly 100 | B |
Pt274 |
MT-ATP6
| m.8993T>C:p.L156P | LS | CC (I, III) | 100 | F |
Pt453 |
MT-ATP6
| m.8993T>G:p.L156R | LS | CC (I, IV) | 100 | F |
Pt341 |
MT-ATP6
| m.8993T>C:p.L156R | LS | ns | 100 | M |
Pt720 |
MT-ATP6
| m.8993T>G:p.L156R | LS | ns | nearly 100 | B |
Pt772 |
MT-ATP6
| m.8993T>G:p.L156R | LS | ns | nearly 100 | M |
Pt968 |
MT-ATP6
| m.8993T>G:p.L156R | LS | ns | nearly 100 | B |
Pt400 |
MT-ATP6
| m.9176T>C:p.L217P | LS | ns | 100 | B |
Pt698 |
MT-ATP6
| m.9176T>C:p.L217P | LS | CIV | 100 | B |
Pt127 |
MT-ATP6
| m.9185T>C:p.L220P | LL | ns | 80 | B |
Pt728 |
MT-ND3
| m.10158T>C:p.S34P | LS | CI | 80 | B |
Pt994 |
MT-ND3
| m.10158T>C:p.S34P | LS | CI | 100 | B |
Pt43 |
MT-ND3
| m.10191T>C:pS45P | LS | CI | 100 | F |
Pt44 |
MT-ND3
| m.10191T>C:pS45P | LS | CI | 69 | F |
Pt58 |
MT-ND3
| m.10191T>C:pS45P | LS | CI | na | |
Pt83 |
MT-ND3
| m.10191T>C:pS45P | LS | CI | 100 | F |
Pt108 |
MT-ND3
| m.10191T>C:p.S45P | LS | CI | 95 | B |
Pt965 |
MT-ND3
| m.10197G>C:pA47P (VUS)b
| LL | CC(I,III,IV) | na | |
Pt190 |
MT-ND4
| m.11246G>A:pA163T (VUS) | LS | CC (I, IV) | 73 | F |
Pt153 |
MT-ND5
| m.13094T>C:pV253A | LS | CC (I, IV) | na | B,M |
Pt467 |
MT-ND5
| m.13513G>A:p.D393N | LL | CI | 59 | B |
Pt744 |
MT-ND5
| m.13513G>A:p.D393N | LL | CC (I, IV) | 50 | B |
Pt377 |
MT-ND6
| m.14439G>A:pP79S | LS | CI | 100 | F |
Pt28 |
MT-ND6
| m.14459G>A:pA72V | LS | CI | 54 | F |
Pt593 |
MT-ND6
| m.14459G>A:p.A72V | LS | CI | 96 | F |
Pt224 |
MT-ND6
| m.14487T>C:p.M63V | LS | CI | 99 | B |
Pt1063 |
MT-ND6
| m.14487T>C:p.M63V | LS | ns | Nearly 100 | B |
Pt396 |
tRNA
Glu
| m.14687A>G | LS | CI | 85 | M |