Introduction
Materials and methods
Study design and population
Statistical analysis
Results
Demographics and family history
Perinatal history
Disease onset and age at diagnostic testing
ID* | Age of onset | Clinical features at onset | Exacerbations/relapses requiring hospitalisation | Survival status | Genetic etiology |
---|---|---|---|---|---|
84
| 5 y 1 m | Hypotonia, mental retardation | No | Alive at 7 y 6 m | Unknown |
66
| 4 y 11 m | Dystonia, spasticity, hyperreflexia | No | Alive at 33 y |
C20orf7
|
94
| 8 y1 m | Dystonia, hypertonia | No | Alive at 18 y 10 m | Unknown |
95
| 18 y 8 m | Gastrointestinal symptoms | Yes | Died at 19 y 6 m | Unknown |
15
| 6 y 7 m | Hypotonia, ophthalmoplegia, fatigue | No | Alive at 14 y 7 m |
MT-ATP6
|
99
| 5 y 9 m | Hypotonia, pos Babinski sign, ophthalmoplegia | Yes | Alive at 33 y | Unknown |
103
| 6 y 5 m | Dystonia, hypertonia, pos Babinski sign | No | Alive at 8 y 6 m | Unknown |
114
| 7 y | Dystonia | No | Lost to follow-up at 10 y | Unknown |
118
| 7 y | Gastrointestinal symptoms | No | Alive at 12 y 5 m | Unknown |
5
| 6 y | Discoordination | No | Alive at 19 y 8 m |
MT-ND3
|
124
| 10 y 5 m | Hypo-hypertonia, dystonia, hypokinesia, dysarthria, hyperreflexia, sucking dysfunction, bradyphrenia | Yes | Alive at 20 y 8 m | Unknown |
127
| 8 y 2 m | Hypertonia, hyperreflexia | No | Alive at 14 y | Unknown |
25
| 19 y | Spasticity, hemiparesis | No | Alive at 58 y |
MT-ATP6
|
Clinical features at onset
Clinical features throughout the disease course
Frequency of affected organs/systems (n = 130) | N | % |
---|---|---|
Abnormal motor findings | 129 | 99.2 |
Abnormal ocular findings | 79 | 60.8 |
Feeding difficulties | 59 | 45.4 |
Epileptic seizures | 51 | 39.2 |
Respiratory dysfunction | 49 | 37.7 |
Mental retardation | 48 | 36.9 |
Sucking dysfunction | 32 | 24.6 |
Hearing dysfunction | 25 | 19.2 |
Cardiac dysfunction | 23 | 17.7 |
Failure to thrive | 21 | 16.2 |
Hepatic dysfunction | 16 | 12.3 |
Microcephaly | 15 | 11.5 |
Peripheral neuropathy | 9 | 6.9 |
Renal dysfunction | 7 | 5.4 |
Haematological dysfunction | 2 | 1.5 |
Abnormal motor findings
Type of abnormal motor findings (n = 130) | N | % |
---|---|---|
Hypotonia | 97 | 74.6 |
Abnormal tendon reflexes§ | 62 | 47.7 |
Dystonia | 58 | 44.6 |
Babinski sign | 55 | 42.3 |
Spasticity | 47 | 36.2 |
Ataxia | 45 | 34.6 |
Hypertonia | 43 | 33.1 |
Muscle weakness | 34 | 26.2 |
Other dyskinetic disorder^ | 27 | 20.8 |
Paresis/palsy | 26 | 20.0 |
Chorea/athetosis | 25 | 19.2 |
Cavus feet | 10 | 7.7 |
Myoclonus | 9 | 6.9 |
Hypokinesia/bradykinesia | 5 | 3.8 |
Abnormal ocular findings
Epileptic seizures
Respiratory dysfunction
Cardiac dysfunction
Other clinical features
Biochemical, histological and genetic findings
ID | Age of onset | B-lactate | CSF-lactate | Complex deficiency | Muscle pathology | Genetic etiology | ID | Age of onset | B-lactate | CSF-lactate | Complex deficiency | Muscle pathology | Genetic etiology |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1
| 3 m | 4.0 | 4.7 | CI | - |
MT -ND1
|
66
| 4 y 11 m | 1.9 | NA | CI | + |
C20orf7
|
2
| 2 y 6 m | 3.0 | 3.9 | CI | + |
MT -ND1
|
67
| 4 y 1 m | 4.6 | NA | CI | + |
C20orf7
|
3
| IU | 2.6 | 2.5 | CI | +§ |
MT-ND3
|
68
| 1 y | NA | NA | CIV | - |
C12orf65
|
4
| 4 m | 8.0 | 6.4 | CI | - |
MT-ND3
|
69
| Perinatal | 10.2 | NA | CI, CII | + |
NDUFA9
|
5
| 6 y | 1.5 | 2.5 | - | - |
MT -ND3
|
70
| 2 m | 4.9 | 2.4 | CI | + |
NDUFA12
|
6
| 1 y | 7.7 | NA | CI, CIV | - |
MT -ND3-4
|
71
| 3 m | 5.7 | NA | CI, CIII | - |
NDUFAF2
|
7
| 11 m | 10.4 | 2.2 | CI, CV | + |
MT -ND5
|
72
| 4 m | NA | NA | CI | - |
NDUFAF2
|
8
| Perinatal | 22.9 | NA | CI, CIII, CIV | + |
MT-ND5
|
73
| 6 m | 4.1 | NA | CI | + |
NDUFV2
|
9
| 8 m | 1.6 | 3.7 | CI | - |
MT -ND5
|
74
| 5 m | 15.0 | NA | CI | - |
NDUFV2
|
10
| 1 y 4 m | 5.0 | 3.2 | CI | + |
MT-ND6
|
75
| 3 y 3 m | 1.6 | NA | CI, CIII | + |
NDUFS7
|
11
| 1 y 9 m | 3.2 | 4.6 | - | + |
MT-ATP6
|
76
| 3 m | 10.2 | 4.7 | CI | - |
NDFUS4
|
12
| 11 m | 2.1 | NA | NA | NA |
MT-ATP6
|
77
| 9 m | 3.6 | 2.0 | CIII | - |
BCS1L
|
13
| 5 m | 4.4 | NA | NA | NA |
MT-ATP6
|
78
| 7 m | 4.2 | 4.0 | CI | + | Unknown |
14
| Perinatal | 8.5 | 5.9 | CV | + |
MT-ATP6
|
79
| 7 m | 1.5 | 1.5 | CII | - | Unknown |
15
| 6 y 7 m | 1.5 | 2.4 | CV | + |
MT-ATP6
|
80
| 6 m | 7.0 | 3.2 | CI | + | Unknown |
16
| 1 y 2 m | 2.1 | 2.7 | CI-IV | - |
MT-ATP6
|
81
| 2 y | 1.0 | 1.9 | - | - | Unknown |
17
| 4 m | 4.7 | 5.2 | CI-IV | + |
MT-ATP6
|
82
| 1 y 3 m | 4.4 | NA | - | + | Unknown |
18
| 2 y 3 m | 1.5 | 2.7 | - | +§ |
MT-ATP6
|
83
| Perinatal | 2.8 | 2.0 | CIV | + | Unknown |
19
| 6 m | 3.1 | 3.3 | - | - |
MT-ATP6
|
84
| 5 y 1 m | 1.1 | 6.1 | NA | NA | Unknown |
20
| 4 m | 2.4 | 3.3 | - | - |
MT-ATP6
|
85
| 1 y 5 m | 2.7 | 2.3 | - | + | Unknown |
21
| 5 m | 5.4 | 5.7 | CI-IV | - |
MT-ATP6
|
86
| 1 y 4 m | 1.2 | NA | - | + | Unknown |
22
| 6 m | 6.2 | 6.2 | CI, CIII, CIV, CV | - |
MT-ATP6
|
87
| Perinatal | 7.5 | 12.9 | CI, CIII | + | Unknown |
23
| 3 m | 5.5 | 5.8 | CV | - |
MT-ATP6
|
88
| 1 y 2 m | 5.5 | 3.0 | CI, CIV | + | Unknown |
24
| 3 m | 6.4 | 8.1 | - | + |
MT-ATP6
|
89
| 7 m | 4.4 | 5.9 | CI, CII | + | Unknown |
25
| 19 y | 1.2 | NA | NA | NA |
MT-ATP6
|
90
| 2 m | 5.6 | 2.1 | CI-III | + | Unknown |
26
| 1 y 6 m | 0.8 | 2.1 | CV | + |
MT-ATP6
|
91
| Perinatal | 17.0 | NA | - | - | Unknown |
27
| 8 m | 8.9 | 2.8 | CI, CIV | + |
MT-TW
|
92
| Perinatal | 6.7 | 3.7 | CI | - | Unknown |
28
| 2 y | 14.8 | 4.0 | CI, CIV | + |
MT-TL1;MT-TE
|
93
| 8 m | NA | NA | CIV | NA | Unknown |
29
| 1 y 4 m | 3.4 | 4.0 | CIV | + |
SURF1
|
94
| 8 y 1 m | NA | NA | CI | - | Unknown |
30
| Perinatal | 5.6 | 6.0 | CIV | + |
SURF1
|
95
| 18 y 8 m | 2.4 | 3.1 | - | - | Unknown |
31
| 1 y | 3.5 | 3.3 | CIV | + |
SURF1
|
96
| 1 y 1 m | NA | NA | - | - | Unknown |
32
| 5 m | 7.8 | 6.0 | CIV | + |
SURF1
|
97
| 3 m | 3.3 | NA | CIV | + | Unknown |
33
| 1 y | 2.6 | NA | CIV | NA |
SURF1
|
98
| 7 m | 5.7 | 3.9 | CI-IV | + | Unknown |
34
| 2 m | NA | NA | CIV | - |
SURF1
|
99
| 5 y 9 m | 2.5 | 3.5 | CI | + | Unknown |
35
| 8 m | NA | NA | CIV | - |
SURF1
|
100
| 1 y | 12.4 | 1.3 | - | - | Unknown |
36
| 5 m | 3.3 | 3.6 | CIV | + |
SURF1
|
101
| Perinatal | 8.4 | 6.3 | CI, CIV | + | Unknown |
37
| 1 m | 3.0 | 3.2 | NA | NA |
SLC19A3
|
102
| 8 m | 0.8 | 1.0 | - | - | Unknown |
38
| 1 m | NA | NA | NA | NA |
SLC19A3
|
103
| 6 y 5 m | 3.1 | 1.8 | CI | NA | Unknown |
39
| Perinatal | 2.1 | NA | NA | NA |
SLC19A3
|
104
| IU | 11.1 | NA | NA | NA | NA |
40
| 6 m | 3.1 | NA | - | + |
SLC19A3
|
105
| 4 m | 4.4 | 3.7 | - | - | Unknown |
41
| 1 m | 4.4 | NA | - | - |
SLC19A3
|
106
| 2 y | 2.9 | 17.0 | CI, CV | + | Unknown |
42
| 1 m | 3.4 | 2.1 | CIV | NA |
SLC19A3
|
107
| Perinatal | 4.8 | 5.5 | CI | - | NA |
43
| 1 m | 3.8 | NA | NA | NA |
SLC19A3
|
108
| 6 m | 1.6 | 2.7 | NA | NA | NA |
44
| 2 y 7 m | 3.3 | 1.2 | - | - |
SLC19A3
|
109
| 3 y | 2.8 | 1.7 | CI-IV | + | Unknown |
45
| 3 m | 2.0 | 1.7 | - | - |
SLC19A3
|
110
| 6 m | 4.7 | 3.1 | CI-IV | +§ | Unknown |
46
| 5 m | 2.1 | NA | - | + |
SUCLA2
|
111
| 7 m | 2.1 | 4.1 | NA | NA | NA |
47
| 1 m | 3.0 | 3.3 | NA | NA |
SUCLA2
|
112
| 7 m | 2.3 | 4.1 | CI-IV | + | Unknown |
48
| 3 m | 5.9 | 2.9 | NA | NA |
SUCLA2
|
113
| Perinatal | 7.9 | 2.8 | CI, CIV | + | Unknown |
49
| 5 m | 1.4 | NA | NA | NA |
SUCLA2
|
114
| 7 y | 2.4 | 1.4 | - | - | Unknown |
50
| 2 m | NA | 6.3 | NA | NA |
SUCLA2
|
115
| 1 m | 0.8 | 4.4 | - | - | Unknown |
51
| 3 m | NA | NA | NA | NA |
SUCLA2
|
116
| 3 y 8 m | 5.7 | 5.0 | - | + | Unknown |
52
| Perinatal | 4.9 | NA | CI, CIII, CIV | NA |
SUCLA2
|
117
| 4 y | 2.1 | 1.8 | - | - | Unknown |
53
| Perinatal | 5.6 | 3.1 | CI, CIV | + |
SUCLA2
|
118
| 7 y | 2.3 | 1.3 | CI | + | Unknown |
54
| IU | 4.3 | NA | CIV | - |
SUCLA2
|
119
| 11 m | 2.6 | NA | - | - | Unknown |
55
| 5 m | 4.5 | 2.8 | CI, CIV | - |
SUCLA2
|
120
| 4 m | 3.9 | 1.2 | - | + | Unknown |
56
| 7 m | 5.0 | 2.1 | CI, CIV | + |
SUCLG1
|
121
| 1 y 8 m | 4.2 | 3.1 | CI | + | Unknown |
57
| 3 m | 5.1 | 4.7 | CI-IV | NA |
SUCLG1
|
122
| 1 y 1 m | 4.3 | NA | - | - | Unknown |
58
| 4 y 7 m | 3.3 | 3.7 | - | - |
PDHA1
|
123
| Perinatal | NA | NA | NA | NA | Unknown |
59
| 10 m | 5.0 | NA | - | - |
PDHA1
|
124
| 10 y 5 m | 3.7 | NA | CI, CIII | + | Unknown |
60
| 1 y 2 m | 3.4 | NA | NA | NA |
PDHA1
|
125
| 5 m | 1.3 | 2.8 | CI | + | NA |
61
| 8 m | 6.2 | 6.2 | CII | - |
PDHA1
|
126
| 2 y 11 m | NA | NA | - | + | Unknown |
62
| 7 m | NA | NA | NA | NA |
PDHA1
|
127
| 8 y 2 m | 4.2 | NA | CI | - | NA |
63
| 8 m | 5.6 | 3.0 | - | + |
SERAC1
|
128
| 4 y 3 m | 1.5 | NA | CI, CIII | + | NA |
64
| Perinatal | 3.8 | 9.1 | CII, CIII | - |
SERAC1
|
129
| 1 y 9 m | 3.9 | 1.5 | CI | - | Unknown |
65
| Perinatal | 2.6 | 3.0 | - | - |
SERAC1
|
130
| 6 m | 8.3 | 5.4 | NA | NA | NA |