Hypotonia with lactic acidemia and hyperammonemia

General Information (adopted from Orphanet):

Synonyms, Signs: COXPD5
Combined oxidative phosphorylation defect type 5
Number of Symptoms 50
OrphanetNr: 137908
OMIM Id: 611719
ICD-10: E88.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 4 cases - PMID: 17873122; 21189481 [IBIS]
Inheritance: Monogenic
Autosomal recessive
- PMID: 17873122; 21189481 [IBIS]
Age of onset: Neonatal
Infancy
- PMID: 17873122; 21189481 [IBIS]

Disease classification (adopted from Orphanet):

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

Comment:

Mutations in the mitochondrial small subunit ribosomal protein MRPS22 (= COXPD5) cause severe, fatal respiratory chain dysfunction due to impaired translation of mitochondrial mRNA. The loss of MRPS22 is accompanied by the loss of most of another small subunit protein MRPS11. In contrast to MRPS16 which is highly conserved and essential for the ribosomal small subunit assembly, MRPS22 has no counterpart in bacteria or yeast and its function is obscure (PMID:18539099).

Symptom Information: Sort by abundance 

1
 (HPO:0100309) Subdural hemorrhage 21189481 IBIS 3 / 7739
2
 (HPO:0002092) Pulmonary hypertension 21189481 IBIS 109 / 7739
3
 (HPO:0000816) Abnormality of Krebs cycle metabolism 21189481 IBIS 3 / 7739
4
 (HPO:0002151) Increased serum lactate 21189481 IBIS 92 / 7739
5
 (HPO:0003128) Lactic acidosis Very frequent [IBIS] 17873122 IBIS 116 / 7739
6
 (HPO:0001942) Metabolic acidosis 21189481 IBIS 81 / 7739
7
 (HPO:0001508) Failure to thrive 21189481 IBIS 454 / 7739
8
 (HPO:0003348) Hyperalaninemia 21189481 IBIS 19 / 7739
9
 (HPO:0001639) Hypertrophic cardiomyopathy Very frequent [IBIS] 17873122; 21189481 IBIS 137 / 7739
10
 (HPO:0002119) Ventriculomegaly 21189481 IBIS 253 / 7739
11
 (HPO:0001716) Wolff-Parkinson-White syndrome 21189481 IBIS 21 / 7739
12
 (HPO:0008972) Decreased activity of mitochondrial respiratory chain Very frequent [IBIS] 17873122; 21189481 IBIS 34 / 7739
13
 (HPO:0011925) Decreased activity of mitochondrial ATP synthase complex Very frequent [IBIS] 17873122 IBIS 10 / 7739
14
 (HPO:0011923) Decreased activity of mitochondrial complex I Very frequent [IBIS] 17873122; 21189481 IBIS 35 / 7739
15
 (HPO:0011924) Decreased activity of mitochondrial complex III Very frequent [IBIS] 17873122; 21189481 IBIS 22 / 7739
16
 (HPO:0008347) Decreased activity of mitochondrial complex IV Very frequent [IBIS] 17873122; 21189481 IBIS 31 / 7739
17
 (HPO:0000969) Edema Very frequent [IBIS] 17873122 IBIS 117 / 7739
18
 (HPO:0001987) Hyperammonemia Very frequent [IBIS] 17873122 IBIS 50 / 7739
19
 (HPO:0001252) Muscular hypotonia Very frequent [IBIS] 17873122; 21189481 IBIS 990 / 7739
20
 (HPO:0001290) Generalized hypotonia 21189481 IBIS 51 / 7739
21
 (HPO:0008947) Infantile muscular hypotonia 17873122 IBIS 482 / 7739
22
 (HPO:0008936) Muscular hypotonia of the trunk 21189481 IBIS 77 / 7739
23
 (HPO:0001319) Neonatal hypotonia 17873122 IBIS 101 / 7739
24
 (HPO:0002352) Leukoencephalopathy 21189481 IBIS 32 / 7739
25
 (HPO:0002510) Spastic tetraplegia 21189481 IBIS 54 / 7739
26
 (HPO:0002374) Diminished movement 21189481 IBIS 1 / 7739
27
 (HPO:0002015) Dysphagia 21189481 IBIS 301 / 7739
28
 (HPO:0011195) EEG with focal sharp slow waves 21189481 IBIS 1 / 7739
29
 (HPO:0001250) Seizures 21189481 IBIS 1245 / 7739
30
 (HPO:0000278) Retrognathia 21189481 IBIS 100 / 7739
31
 (HPO:0000252) Microcephaly 21189481 IBIS 832 / 7739
32
 (HPO:0002079) Hypoplasia of the corpus callosum 21189481 IBIS 161 / 7739
33
 (HPO:0000664) Synophrys 21189481 IBIS 112 / 7739
34
 (HPO:0001541) Ascites 17873122 IBIS 94 / 7739
35
 (HPO:0000047) Hypospadias 21189481 IBIS 250 / 7739
36
 (HPO:0005989) Redundant neck skin 21189481 IBIS 40 / 7739
37
 (HPO:0000369) Low-set ears 21189481 IBIS 372 / 7739
38
 (HPO:0000358) Posteriorly rotated ears 21189481 IBIS 163 / 7739
39
 (HPO:0000091) Abnormality of the renal tubule 17873122 IBIS 15 / 7739
40
 (HPO:0001510) Growth delay 21189481 IBIS 295 / 7739
41
 (HPO:0001522) Death in infancy 17873122 IBIS 275 / 7739
42
 (HPO:0012448) Delayed myelination 21189481 IBIS 51 / 7739
43
 (HPO:0003811) Neonatal death 17873122 IBIS 44 / 7739
44
 (MedDRA:10048978) Gastrostomy 21189481 IBIS 1 / 7739
45
 (OMIM) Dilatation of the 3rd ventricle (in one family) 21189481 IBIS 2 / 7739
46
 (OMIM) Edema, nonpitting 21189481 IBIS 3 / 7739
47
 (OMIM) Increased serum ammonia 17873122 IBIS 5 / 7739
48
 (OMIM) Metabolic acidosis, severe 21189481 IBIS 2 / 7739
49
 (OMIM) Skeletal muscle shows decreased activities of mitochondrial respiratory complexes I, III, IV, and V 17873122 IBIS 1 / 7739
50
 (OMIM) Tubulopathy (1 family) 17873122 IBIS 1 / 7739

Associated genes:

MRPS22;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Saada et al. (2007) reported 3 sibs, born of consanguineous parents, with antenatal onset of a severe mitochondrial disorder. Late in gestation, ultrasound showed generalized edema, especially of the neck, labia, and palms, with prominent subcutaneous edema and ...
Molecular genetics OMIM By homozygosity mapping, followed by sequence analysis, Saada et al. (2007) identified a homozygous mutation in the MRPS22 gene (605810.0001) in 3 sibs with combined mitochondrial oxidative phosphorylation deficiency. In vitro studies showed that recombinant MRPS22 restored COX ...