Myopathy, lactic acidosis, and sideroblastic anemia 2; MLASA2

General Information (adopted from Orphanet):

Synonyms, Signs:
Number of Symptoms 26
OrphanetNr:
OMIM Id: 613561
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 11 cases - PMID: 25638461 [IBIS]
Inheritance: Autosomal recessive
- PMID: 25638461 [IBIS]
Age of onset: Infancy
childhood
- PMID: 25638461 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Mitochondrial myopathy and sideroblastic anemia
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare hematologic disease
 -Rare neurologic disease

Comment:

The p.Ser435Gly (c.1303A>G) mutation is located at the ribosomal protein S4-like domain of the gene, while other reported YARS2 mutations are all within the catalytic domain e.g. (p.Phe52Leu). The proband with p.Ser435Gly mutation showed more severe symptoms and an earlier onset than previously reported patients (PMID:24430573).

Symptom Information: Sort by abundance 

1
(HPO:0000508) Ptosis 23918765 IBIS 459 / 7739
2
(HPO:0001488) Bilateral ptosis 23918765 IBIS 42 / 7739
3
(HPO:0002015) Dysphagia 24344687 IBIS 301 / 7739
4
(HPO:0002240) Hepatomegaly 24344687 IBIS 467 / 7739
5
(HPO:0002910) Elevated hepatic transaminases 24344687 IBIS 158 / 7739
6
(HPO:0001508) Failure to thrive 23918765 IBIS 454 / 7739
7
(HPO:0001510) Growth delay 23918765 IBIS 295 / 7739
8
(HPO:0001639) Hypertrophic cardiomyopathy 25638461 IBIS 137 / 7739
9
(HPO:0001924) Sideroblastic anemia Very frequent [IBIS] 25638461 IBIS 12 / 7739
10
(HPO:0001873) Thrombocytopenia 25638461 IBIS 224 / 7739
11
(HPO:0001875) Neutropenia 25638461 IBIS 83 / 7739
12
(HPO:0011924) Decreased activity of mitochondrial complex III 25638461 IBIS 22 / 7739
13
(HPO:0002151) Increased serum lactate Very frequent [IBIS] 25638461 IBIS 92 / 7739
14
(HPO:0003128) Lactic acidosis Very frequent [IBIS] 25638461 IBIS 116 / 7739
15
(HPO:0011923) Decreased activity of mitochondrial complex I 25638461 IBIS 35 / 7739
16
(HPO:0008347) Decreased activity of mitochondrial complex IV 25638461 IBIS 31 / 7739
17
(HPO:0002747) Respiratory insufficiency due to muscle weakness 24344687 IBIS 48 / 7739
18
(HPO:0003546) Exercise intolerance 23918765 IBIS 62 / 7739
19
(HPO:0003202) Skeletal muscle atrophy 23918765 IBIS 281 / 7739
20
(HPO:0003323) Progressive muscle weakness 24344687 IBIS 17 / 7739
21
(HPO:0003737) Mitochondrial myopathy Frequent [IBIS] 25638461 IBIS 18 / 7739
22
(HPO:0100295) Muscle fiber atrophy 25638461 IBIS 22 / 7739
23
(HPO:0003700) Generalized amyotrophy 23918765 IBIS 39 / 7739
24
(OMIM) Rare ragged red fibers 20598274 IBIS 1 / 7739
25
(OMIM) Skeletal muscle biopsy shows subsarcolemmal mitochondrial aggregates 20598274 IBIS 1 / 7739
26
(OMIM) Decreased cytochrome C oxidase activity 20598274 IBIS 2 / 7739

Associated genes:

YARS2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Riley et al. (2010) reported 2 sibs, born of consanguineous Lebanese parents, with MLASA2. Both developed transfusion-dependent sideroblastic anemia in infancy, followed by progressive lethargy, muscle weakness, and exercise intolerance in childhood associated with persistent lactic acidemia. The ...
Molecular genetics OMIM By genomewide linkage analysis followed by candidate gene sequencing of 2 consanguineous Lebanese families with MLASA2, Riley et al. (2010) identified a homozygous mutation in the YARS2 gene (F52L; 610957.0001). In vitro functional expression assays showed that the ...