Myopathy, lactic acidosis, and sideroblastic anemia 1; MLASA1

General Information (adopted from Orphanet):

Synonyms, Signs: Mitochondrial myopathy and sideroblastic anemia
Number of Symptoms 55
OrphanetNr:
OMIM Id: 600462
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 5 cases - PMID: 26556812 [IBIS]
Inheritance: Autosomal recessive
- PMID: 15971356 [IBIS]
Age of onset: Childhood
- PMID: 26556812 [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:

PUS1, pseudouridylate synthase 1, an enzyme located in both nucleus and mitochondria, which converts uridine into pseudouridine in several cytosolic and mitochondrial tRNA positions and increases the efficiency of protein synthesis in both compartments (PMID:21686963). The most common cause of MLASA seems to be mutations in YARS2 (OMIM: 613561, MLASA2), while to date, only four PUS1 mutations have been reported, the missense p.Arg116Trp found in the homozygous state in three families, the missense p.Arg295Trp found in a Turkish family, and the nonsense p.Glu200* found in the homozygous state in another family. Two novel different mutations in the PUS1 gene were identified: c.487delA (p.I163Lfs*4) and c.884 G>A (p.R295Q) (PMID:26556812).

Symptom Information: Sort by abundance 

1
 (HPO:0007377) Abnormality of somatosensory evoked potentials 26556812 IBIS 2 / 7739
2
 (HPO:0001272) Cerebellar atrophy 26556812 IBIS 197 / 7739
3
 (HPO:0002059) Cerebral atrophy 26556812 IBIS 171 / 7739
4
 (HPO:0001639) Hypertrophic cardiomyopathy 26556812 IBIS 137 / 7739
5
 (HPO:0002093) Respiratory insufficiency 26556812 IBIS 410 / 7739
6
 (HPO:0000407) Sensorineural hearing impairment 26556812 IBIS 524 / 7739
7
 (HPO:0001288) Gait disturbance 26556812 IBIS 318 / 7739
8
 (HPO:0000278) Retrognathia 15971356 IBIS 100 / 7739
9
 (HPO:0000212) Gingival overgrowth 15971356 IBIS 43 / 7739
10
 (HPO:0000322) Short philtrum 15971356 IBIS 130 / 7739
11
 (HPO:0002058) Myopathic facies 15971356 IBIS 26 / 7739
12
 (HPO:0000316) Hypertelorism 21686963 IBIS 644 / 7739
13
 (HPO:0009743) Distichiasis 7726239 IBIS 9 / 7739
14
 (HPO:0000218) High palate 7726239 IBIS 356 / 7739
15
 (HPO:0000331) Short chin 7726239 IBIS 33 / 7739
16
 (HPO:0009117) Aplasia/Hypoplasia of the maxilla 7726239 IBIS 18 / 7739
17
 (HPO:0000252) Microcephaly 21686963 IBIS 832 / 7739
18
 (HPO:0000347) Micrognathia 7726239 IBIS 426 / 7739
19
 (HPO:0000327) Hypoplasia of the maxilla 7726239 IBIS 129 / 7739
20
 (HPO:0003196) Short nose 15971356 IBIS 264 / 7739
21
 (HPO:0000504) Abnormality of vision 21686963 IBIS 22 / 7739
22
 (HPO:0001131) Corneal dystrophy 26556812 IBIS 56 / 7739
23
 (HPO:0001263) Global developmental delay 15971356 IBIS 853 / 7739
24
 (HPO:0100543) Cognitive impairment 21686963 IBIS 230 / 7739
25
 (HPO:0001270) Motor delay 15971356 IBIS 322 / 7739
26
 (HPO:0001249) Intellectual disability 21686963 IBIS 1089 / 7739
27
 (HPO:0000823) Delayed puberty 14981724 IBIS 65 / 7739
28
 (HPO:0003691) Scapular winging 21686963 IBIS 51 / 7739
29
 (HPO:0002751) Kyphoscoliosis 14981724 IBIS 131 / 7739
30
 (HPO:0003307) Hyperlordosis 21686963 IBIS 122 / 7739
31
 (HPO:0001510) Growth delay 21686963 IBIS 295 / 7739
32
 (HPO:0000980) Pallor 14981724 IBIS 52 / 7739
33
 (HPO:0001935) Microcytic anemia 14981724 IBIS 32 / 7739
34
 (HPO:0001931) Hypochromic anemia 14981724 IBIS 5 / 7739
35
 (HPO:0012132) Erythroid hyperplasia 14981724 IBIS 4 / 7739
36
 (HPO:0001924) Sideroblastic anemia Very frequent [IBIS] 15971356 IBIS 12 / 7739
37
 (HPO:0011923) Decreased activity of mitochondrial complex I 15971356 IBIS 35 / 7739
38
 (HPO:0008306) Abnormal iron deposition in mitochondria 7726239 IBIS 2 / 7739
39
 (HPO:0008347) Decreased activity of mitochondrial complex IV 15971356 IBIS 31 / 7739
40
 (HPO:0003281) Increased serum ferritin 14981724 IBIS 32 / 7739
41
 (HPO:0002151) Increased serum lactate 14981724 IBIS 92 / 7739
42
 (HPO:0003128) Lactic acidosis Very frequent [IBIS] 15971356 IBIS 116 / 7739
43
 (HPO:0003688) Decreased activity of cytochrome C oxidase in muscle tissue 14981724 IBIS 20 / 7739
44
 (HPO:0012240) Increased intramyocellular lipid droplets 14981724 IBIS 7 / 7739
45
 (HPO:0003546) Exercise intolerance 15971356 IBIS 62 / 7739
46
 (HPO:0003323) Progressive muscle weakness 14981724 IBIS 17 / 7739
47
 (HPO:0009055) Generalized limb muscle atrophy 21686963 IBIS 4 / 7739
48
 (HPO:0001252) Muscular hypotonia 21686963 IBIS 990 / 7739
49
 (HPO:0003737) Mitochondrial myopathy Very frequent [IBIS] 15971356 IBIS 18 / 7739
50
 (HPO:0003202) Skeletal muscle atrophy 21686963; 26556812 IBIS 281 / 7739
51
 (OMIM) High philtrum (1 family) 7726239 IBIS 1 / 7739
52
 (OMIM) Skeletal muscle biopsy shows fat droplets in sarcoplasm and mitochondria 14981724 IBIS 1 / 7739
53
 (OMIM) Ringed sideroblasts on peripheral smear and bone marrow 15971356 IBIS 1 / 7739
54
 (OMIM) Pappenheimer bodies 14981724 IBIS 1 / 7739
55
 (OMIM) Mitochondrial paracrystalline inclusion bodies 15971356 IBIS 1 / 7739

Associated genes:

PUS1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Myopathy, lactic acidosis, and sideroblastic anemia (MLASA) is a rare autosomal recessive oxidative phosphorylation disorder specific to skeletal muscle and bone marrow (Bykhovskaya et al., 2004).

- Genetic Heterogeneity of MLASA

MLASA2 (613561) is ...
Clinical Description OMIM Rawles and Weller (1974) reported 2 brothers with myopathy, lactic acidosis, and sideroblastic anemia with ringed sideroblasts. Both reported exercise intolerance beginning in childhood. The first was studied at age 19 because of breathlessness on exertion and ankle ...
Molecular genetics OMIM By sequence analysis of each of the 6 known genes in the 12q24.33 MLASA candidate region defined by Casas et al. (2004), as well as of 4 putative genes with expression in bone marrow or muscle, Bykhovskaya et ...