Mitochondrial encephalo-cardio-myopathy due to TMEM70 deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: MC5DN2
Mitochondrial Complex V (ATP Synthase) Deficiency, TMEM70 type
Mitochondrial encephalo-cardio-myopathy due to ATP synthase deficiency
Mitochondrial encephalo-cardio-myopathy due to mitochondrial respiratory chain complex V deficiency
Encephalocardiomyopathy, mitochondrial, neonatal, due to ATP Synthase Deficiency
Mitochondrial encephalo-cardio-myopathy due to F1Fo ATPase deficiency
Number of Symptoms 116
OrphanetNr: 1194
OMIM Id: 614052
ICD-10: G71.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Monogenic
Autosomal recessive
18953340 [IBIS]
Age of onset: Neonatal
Childhood
Infancy
18953340; 25326274 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Mitochondrial disorder due to a defect in assembly or maturation of the respiratory chain complexes
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Comment:

TMEM70 (MC5DN2) mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy (PMID:18953340). TMEM70 deficiency is a panethnic, multisystemic disease with variable outcome depending mainly on adequate management of hyperammonaemic crises in the neonatal period and early childhood.Ten-year survival was 63 %, importantly for prognostication, no child died after the age of five years (PMID:25326274).

Symptom Information: Sort by abundance 

1
 (HPO:0008872) Feeding difficulties in infancy Frequent [IBIS] 25326274 IBIS 153 / 7739
2
 (HPO:0002013) Vomiting Occasional [IBIS] 26% (n=39) 25326274 IBIS 191 / 7739
3
 (HPO:0000518) Cataract Occasional [IBIS] 11% (n=45) 25326274 IBIS 454 / 7739
4
 (HPO:0000580) Pigmentary retinopathy Occasional [IBIS] 9% (n=45) 25326274 IBIS 49 / 7739
5
 (HPO:0000486) Strabismus Occasional [IBIS] 16% (n=45) 25326274 IBIS 576 / 7739
6
 (HPO:0000646) Amblyopia Rare [IBIS] 4% (n=45) 25326274 IBIS 42 / 7739
7
 (HPO:0000508) Ptosis 25326274 IBIS 459 / 7739
8
 (HPO:0002092) Pulmonary hypertension Occasional [IBIS] 22% (n=45) 25326274 IBIS 109 / 7739
9
 (HPO:0002093) Respiratory insufficiency Frequent [IBIS] Frequent [Orphanet] 54% (n=48) 25326274 IBIS 410 / 7739
10
 (HPO:0002151) Increased serum lactate 25326274 IBIS 92 / 7739
11
 (HPO:0003128) Lactic acidosis Frequent [IBIS] 25326274 IBIS 116 / 7739
12
 (HPO:0001942) Metabolic acidosis 25326274 IBIS 81 / 7739
13
 (HPO:0001947) Renal tubular acidosis 25326274 IBIS 21 / 7739
14
 (HPO:0004322) Short stature Frequent [IBIS] 89% (n=38) 25326274 IBIS 1232 / 7739
15
 (HPO:0004325) Decreased body weight Frequent [Orphanet] 21147908 IBIS 492 / 7739
16
 (HPO:0001508) Failure to thrive 21147908 IBIS 454 / 7739
17
 (HPO:0003074) Hyperglycemia Occasional [IBIS] 25326274 IBIS 37 / 7739
18
 (HPO:0001943) Hypoglycemia Occasional [IBIS] 25326274 IBIS 131 / 7739
19
 (HPO:0002173) Hypoglycemic seizures 25326274 IBIS 19 / 7739
20
 (HPO:0003535) 3-Methylglutaconic aciduria Frequent [IBIS] 25326274 IBIS 10 / 7739
21
 (HPO:0003215) Dicarboxylic aciduria 25326274 IBIS 7 / 7739
22
 (HPO:0001631) Atria septal defect Occasional [IBIS] 10% (n=42) 25326274 IBIS 274 / 7739
23
 (HPO:0001646) Abnormality of the aortic valve Frequent [Orphanet] 25326274 IBIS 55 / 7739
24
 (HPO:0001647) Bicuspid aortic valve Rare [IBIS] 5% (n=42) 25326274 IBIS 34 / 7739
25
 (HPO:0001638) Cardiomyopathy Frequent [IBIS] Frequent [Orphanet] 89% (n=45) 25326274 IBIS 192 / 7739
26
 (HPO:0001639) Hypertrophic cardiomyopathy Frequent [IBIS] 84% (n=45) 25326274 IBIS 137 / 7739
27
 (HPO:0001644) Dilated cardiomyopathy Rare [IBIS] 4% (n=45) 25326274 IBIS 141 / 7739
28
 (HPO:0001680) Coarctation of aorta Rare [IBIS] 5% (n=42) 25326274 IBIS 57 / 7739
29
 (HPO:0001642) Pulmonic stenosis Occasional [IBIS] 16% (n=45) 25326274 IBIS 89 / 7739
30
 (HPO:0001716) Wolff-Parkinson-White syndrome Occasional [IBIS] 13% (n=45) 25326274 IBIS 21 / 7739
31
 (HPO:0001635) Congestive heart failure Frequent [IBIS] Frequent [Orphanet] 25326274 IBIS 232 / 7739
32
 (HPO:0011925) Decreased activity of mitochondrial ATP synthase complex Frequent [IBIS] 82% (n=11) 25326274 IBIS 10 / 7739
33
 (HPO:0011923) Decreased activity of mitochondrial complex I Frequent [IBIS] 48% (n=21) 25326274 IBIS 35 / 7739
34
 (HPO:0008347) Decreased activity of mitochondrial complex IV Frequent [IBIS] 33% (n=21) 25326274 IBIS 31 / 7739
35
 (HPO:0002902) Hyponatremia Occasional [IBIS] 25326274 IBIS 37 / 7739
36
 (HPO:0001939) Abnormality of metabolism/homeostasis Very frequent [IBIS] 93% (n=44) 25326274 IBIS 328 / 7739
37
 (HPO:0001987) Hyperammonemia Frequent [IBIS] Very frequent [Orphanet] 25326274 IBIS 50 / 7739
38
 (HPO:0002149) Hyperuricemia 25326274 IBIS 37 / 7739
39
 (HPO:0001252) Muscular hypotonia Very frequent [IBIS] Very frequent [Orphanet] 95% (n=42) 25326274 IBIS 990 / 7739
40
 (HPO:0008947) Infantile muscular hypotonia Frequent [IBIS] 25326274 IBIS 482 / 7739
41
 (HPO:0001324) Muscle weakness 20728387 IBIS 859 / 7739
42
 (HPO:0003326) Myalgia 25326274 IBIS 143 / 7739
43
 (HPO:0003738) Exercise-induced myalgia 25326274 IBIS 19 / 7739
44
 (HPO:0001298) Encephalopathy 21147908 IBIS 72 / 7739
45
 (HPO:0001251) Ataxia 25326274 IBIS 413 / 7739
46
 (HPO:0002066) Gait ataxia 21147908 IBIS 327 / 7739
47
 (HPO:0007034) Generalized hyperreflexia 25326274 IBIS 33 / 7739
48
 (HPO:0002376) Developmental regression 25326274 IBIS 74 / 7739
49
 (HPO:0001263) Global developmental delay Very frequent [IBIS] 98% (n=40) 25326274 IBIS 853 / 7739
50
 (HPO:0001249) Intellectual disability 25326274 IBIS 1089 / 7739
51
 (HPO:0010864) Intellectual disability, severe 25326274 IBIS 120 / 7739
52
 (HPO:0001270) Motor delay 21147908 IBIS 322 / 7739
53
 (HPO:0001254) Lethargy Frequent [IBIS] 25326274 IBIS 104 / 7739
54
 (HPO:0000733) Stereotypy 25326274 IBIS 58 / 7739
55
 (HPO:0001337) Tremor 25326274 IBIS 200 / 7739
56
 (HPO:0001265) Hyporeflexia 25326274 IBIS 208 / 7739
57
 (HPO:0001250) Seizures Frequent [Orphanet] 25326274 IBIS 1245 / 7739
58
 (HPO:0002197) Generalized seizures 25326274 IBIS 30 / 7739
59
 (HPO:0002133) Status epilepticus 25326274 IBIS 59 / 7739
60
 (HPO:0001511) Intrauterine growth retardation Frequent [IBIS] Frequent [Orphanet] 47% (n=43) 25326274 IBIS 358 / 7739
61
 (HPO:0001562) Oligohydramnios Frequent [IBIS] Very frequent [Orphanet] 40% (n=35) 25326274 IBIS 75 / 7739
62
 (HPO:0010442) Polydactyly 25326274 IBIS 69 / 7739
63
 (HPO:0001233) 2-3 finger syndactyly 25326274 IBIS 7 / 7739
64
 (HPO:0001762) Talipes equinovarus 25326274 IBIS 309 / 7739
65
 (HPO:0000308) Microretrognathia 25326274 IBIS 78 / 7739
66
 (HPO:0005469) Flat occiput 21147908 IBIS 30 / 7739
67
 (HPO:0000348) High forehead 25326274 IBIS 157 / 7739
68
 (HPO:0000252) Microcephaly Frequent [IBIS] Very frequent [Orphanet] 71% (n=41) 25326274 IBIS 832 / 7739
69
 (HPO:0011451) Congenital microcephaly 25326274 IBIS 6 / 7739
70
 (HPO:0001274) Agenesis of corpus callosum 25326274 IBIS 142 / 7739
71
 (HPO:0002079) Hypoplasia of the corpus callosum 25326274 IBIS 161 / 7739
72
 (HPO:0007733) Laterally curved eyebrow 25326274 IBIS 2 / 7739
73
 (HPO:0002240) Hepatomegaly Frequent [Orphanet] 25326274 IBIS 467 / 7739
74
 (HPO:0006582) Reye syndrome-like episodes 20728387 IBIS 5 / 7739
75
 (HPO:0001537) Umbilical hernia 25326274 IBIS 206 / 7739
76
 (HPO:0000023) Inguinal hernia 25326274 IBIS 181 / 7739
77
 (HPO:0000823) Delayed puberty 25326274 IBIS 65 / 7739
78
 (HPO:0000039) Epispadias 25326274 IBIS 7 / 7739
79
 (HPO:0000047) Hypospadias Frequent [IBIS] Frequent [Orphanet] 50% (n=26) 25326274 IBIS 250 / 7739
80
 (HPO:0000028) Cryptorchidism Frequent [IBIS] 67% (n=14) 20335238 IBIS 347 / 7739
81
 (HPO:0000035) Abnormality of the testis Frequent [Orphanet] 20335238 IBIS 296 / 7739
82
 (HPO:0001999) Abnormal facial shape Frequent [IBIS] 66% (n=41) 25326274 IBIS 169 / 7739
83
 (HPO:0000494) Downslanted palpebral fissures 25326274 IBIS 328 / 7739
84
 (HPO:0002009) Potter facies 25326274 IBIS 8 / 7739
85
 (HPO:0000343) Long philtrum 21147908 IBIS 262 / 7739
86
 (HPO:0000233) Thin vermilion border 25326274 IBIS 124 / 7739
87
 (HPO:0000431) Wide nasal bridge 25326274 IBIS 290 / 7739
88
 (HPO:0000707) Abnormality of the nervous system 21147908 IBIS 61 / 7739
89
 (HPO:0000357) Abnormal location of ears Very frequent [Orphanet] 21147908 IBIS 328 / 7739
90
 (HPO:0000369) Low-set ears 25326274 IBIS 372 / 7739
91
 (HPO:0000358) Posteriorly rotated ears 21147908 IBIS 163 / 7739
92
 (HPO:0002104) Apnea 25326274 IBIS 106 / 7739
93
 (HPO:0000077) Abnormality of the kidney Occasional [Orphanet] 25326274 IBIS 73 / 7739
94
 (HPO:0000126) Hydronephrosis 25326274 IBIS 119 / 7739
95
 (HPO:0000112) Nephropathy 25326274 IBIS 92 / 7739
96
 (HPO:0000083) Renal insufficiency Frequent [IBIS] 34% (n=45) 25326274 IBIS 232 / 7739
97
 (HPO:0005301) Persistent left superior vena cava Rare [IBIS] 2% (n=42) 25326274 IBIS 4 / 7739
98
 (HPO:0001371) Flexion contracture 25326274 IBIS 220 / 7739
99
 (HPO:0001510) Growth delay Very frequent [IBIS] 94% (n=35) 25326274 IBIS 295 / 7739
100
 (HPO:0000365) Hearing impairment Rare [IBIS] 4% (n=45) 25326274 IBIS 539 / 7739
101
 (HPO:0001622) Premature birth Frequent [IBIS] 75% (n=48) 25326274 IBIS 100 / 7739
102
 (HPO:0040086) Abnormal prolactin level 25326274 IBIS 2 / 7739
103
 (HPO:0030680) Abnormality of cardiovascular system morphology Very frequent [IBIS] 93% (n=45) 25326274 IBIS 355 / 7739
104
 (HPO:0002500) Abnormality of the cerebral white matter 25326274 IBIS 73 / 7739
105
 (HPO:0001273) Abnormality of the corpus callosum 25326274 IBIS 20 / 7739
106
 (HPO:0001272) Cerebellar atrophy 25326274 IBIS 197 / 7739
107
 (HPO:0002120) Cerebral cortical atrophy Frequent [Orphanet] 25326274 IBIS 187 / 7739
108
 (HPO:0003819) Death in childhood 25326274 IBIS 42 / 7739
109
 (HPO:0001522) Death in infancy Frequent [Orphanet] 25326274 IBIS 275 / 7739
110
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 21147908 IBIS 949 / 7739
111
 (HPO:0006879) Pontocerebellar atrophy 25326274 IBIS 6 / 7739
112
 (OMIM) Decreased mitochondrial complex V activity 25326274 IBIS 1 / 7739
113
 (OMIM) Hyperlactatemia 25326274 IBIS 3 / 7739
114
 (OMIM) Motor dyspraxia 25326274 IBIS 2 / 7739
115
 (OMIM) Pseudoobstruction 25326274 IBIS 2 / 7739
116
 (OMIM) Respiratory insufficiency at birth 25326274 IBIS 1 / 7739

Associated genes:

TMEM70;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Cizkova et al. (2008) reported 8 children from 6 Romani Gypsy families with neonatal mitochondrial encephalocardiomyopathy associated with ATP synthase deficiency. Clinical features included psychomotor retardation, microcephaly, hypotonia, growth retardation, hypertrophic cardiomyopathy, dysmorphism, hypospadias, lactic acidosis, and 3-methylglutaconic ...
Molecular genetics OMIM In affected individuals from 6 Romani Gypsy families with neonatal mitochondrial encephalocardiomyopathy associated with ATP synthase deficiency, Cizkova et al. (2008) identified a homozygous mutation in the TMEM70 gene (612418.0001). The same homozygous mutation was identified in 23 ...