Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: COXPD10
Combined OXPHOS deficiency type 10
Combined OXPHOS defect type 10
Combined oxidative phosphorylation defect type 10
Cardiomyopathy, infantile hypertrophic mitochondrial, and lactic acidosis
Number of Symptoms 30
OrphanetNr: 314637
OMIM Id: 614702
ICD-10: I42.2
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: < 0.1 of 100 000
Inheritance: Autosomal recessive
Monogenic
22608499 [IBIS]
Age of onset: Neonatal
Infancy
23929671 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Mitochondrial disease with hypertrophic cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Mitochondrial disorder due to a defect in mitochondrial protein synthesis
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Mitochondrial-tRNA modifier 1 (MTO1) mutations are commonly associated with a presentation of hypertrophic cardiomyopathy, lactic acidosis, and mitochondrial respiratory chain (MRC) deficiency. The age of onset is between birth and 5 month (PMID:23929671). An autosomal-recessive mode of inheritance is assumed in Ghezzi et al. (2012).

Symptom Information: Sort by abundance 

1
 (HPO:0011968) Feeding difficulties Occasional [IBIS] 25% (n=8) 23929671 IBIS 240 / 7739
2
 (HPO:0000648) Optic atrophy Occasional [IBIS] 12.5% (n=8) 23929671 IBIS 238 / 7739
3
 (HPO:0011951) Aspiration pneumonia Occasional [IBIS] 12.5% (n=8) 23929671 IBIS 6 / 7739
4
 (HPO:0002151) Increased serum lactate 22608499 IBIS 92 / 7739
5
 (HPO:0003128) Lactic acidosis Very frequent [IBIS] 100% (n=8) 23929671 IBIS 116 / 7739
6
 (HPO:0001942) Metabolic acidosis 22608499 IBIS 81 / 7739
7
 (HPO:0001508) Failure to thrive Occasional [IBIS] 25% (n=8) 23929671 IBIS 454 / 7739
8
 (HPO:0001518) Small for gestational age 22608499 IBIS 107 / 7739
9
 (HPO:0001943) Hypoglycemia Occasional [IBIS] 12.5% (n=8) 23929671 IBIS 131 / 7739
10
 (HPO:0003348) Hyperalaninemia Frequent [IBIS] 37.5% (n=8) 23929671 IBIS 19 / 7739
11
 (HPO:0001639) Hypertrophic cardiomyopathy Very frequent [IBIS] 100% (n=8) 23929671 IBIS 137 / 7739
12
 (HPO:0011675) Arrhythmia 22608499 IBIS 226 / 7739
13
 (HPO:0001688) Sinus bradycardia Occasional [IBIS] 12.5% (n=8) 23929671 IBIS 18 / 7739
14
 (HPO:0001716) Wolff-Parkinson-White syndrome Occasional [IBIS] 12.5% (n=8) 23929671 IBIS 21 / 7739
15
 (HPO:0001649) Tachycardia Occasional [IBIS] 12.5% (n=8) 23929671 IBIS 53 / 7739
16
 (HPO:0001635) Congestive heart failure 22608499 IBIS 232 / 7739
17
 (HPO:0008972) Decreased activity of mitochondrial respiratory chain 23929671 IBIS 34 / 7739
18
 (HPO:0001252) Muscular hypotonia Frequent [IBIS] 50% (n=8) 23929671 IBIS 990 / 7739
19
 (HPO:0008947) Infantile muscular hypotonia Very frequent 100% (n=8) 23929671 IBIS 482 / 7739
20
 (HPO:0001324) Muscle weakness Occasional 12.5% (n=8) 23929671 IBIS 859 / 7739
21
 (HPO:0001298) Encephalopathy Occasional [IBIS] 12.5% (n=8) 23929671 IBIS 72 / 7739
22
 (HPO:0001332) Dystonia Occasional [IBIS] 12.5% (n=8) 23929671 IBIS 197 / 7739
23
 (HPO:0001263) Global developmental delay Occasional [IBIS] 25% (n=8) 23929671 IBIS 853 / 7739
24
 (HPO:0001270) Motor delay Occasional [IBIS] 25% (n=8) 23929671 IBIS 322 / 7739
25
 (HPO:0001250) Seizures Occasional [IBIS] 12.5% (n=8) 23929671 IBIS 1245 / 7739
26
 (HPO:0002919) Ketonuria Occasional [IBIS] 12.5% (n=8) 23929671 IBIS 18 / 7739
27
 (HPO:0001510) Growth delay 22608499 IBIS 295 / 7739
28
 (OMIM) Lack of ocular fixation (1 patient) Occasional 12.5% (n=8) 23929671 IBIS 1 / 7739
29
 (OMIM) T2-weighted hyperintensities in deep brain regions 23929671 IBIS 1 / 7739
30
 (OMIM) Variable deficiencies of mitochondrial respiratory chain complexes I, III, and IV 22608499 IBIS 1 / 7739

Associated genes:

MTO1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
MTO1 rs143747297 pathogenic RCV000029168.4
MTO1 rs201544686 pathogenic RCV000074506.2
MTO1 rs397518449 pathogenic RCV000029167.5
MTO1 rs398122419 pathogenic RCV000074507.2

Additional Information:

Description: (OMIM) COXPD10 is an autosomal recessive disorder resulting in variable defects of mitochondrial oxidative respiration. Affected individuals present in infancy with hypertrophic cardiomyopathy and lactic acidosis. The severity is variable, but can be fatal in the most severe cases ...
Clinical Description OMIM Ghezzi et al. (2012) reported 2 Italian sibs, born of unrelated parents, with fatal infantile hypertrophic cardiomyopathy. Both patients showed reduced fetal growth. The first presented soon after birth with lactic acidosis and severe hypoglycemia. Electroencephalogram (EEG) and ...
Molecular genetics OMIM By whole-exome sequencing of an Italian patient with COXPD10 manifest as fatal infantile hypertrophic cardiomyopathy and lactic acidosis, Ghezzi et al. (2012) identified compound heterozygous mutations in the MTO1 gene (1858dup, 614667.0001 and A428T, 614667.0002). The patient's similarly ...