NEMMLAS
MCID: NRD036
MIFTS: 21

Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures (NEMMLAS)

Categories: Genetic diseases, Neuronal diseases

Aliases & Classifications for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

MalaCards integrated aliases for Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures:

Name: Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures 57 75 29 6
Nemmlas 57 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype and severity
onset in early infancy


HPO:

32
neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures:
Onset and clinical course phenotypic variability


Classifications:



Summaries for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

UniProtKB/Swiss-Prot : 75 Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures: An autosomal recessive, mitochondrial disorder with a broad phenotypic spectrum ranging from severe neonatal lactic acidosis, encephalomyopathy and early death to an attenuated course with milder manifestations. Clinical features include delayed psychomotor development, intellectual disability, hypotonia, dystonia, ataxia, and spasticity. Severe combined respiratory chain deficiency may be found in severely affected individuals.

MalaCards based summary : Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures, is also known as nemmlas. An important gene associated with Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures is WARS2 (Tryptophanyl TRNA Synthetase 2, Mitochondrial). Affiliated tissues include skeletal muscle, and related phenotypes are nystagmus and intellectual disability

OMIM : 57 NEMMLAS is an autosomal recessive multisystemic disorder characterized by delayed psychomotor development, intellectual disability, and abnormal motor function, including hypotonia, dystonia, ataxia, and spasticity. Patient tissues may show deficiencies in one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes, but this is not a constant finding (summary by Wortmann et al., 2017). (617710)

Related Diseases for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

Symptoms & Phenotypes for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
optic atrophy
strabismus
amblyopia
exotropia
more
Muscle Soft Tissue:
muscle weakness
limb hypertonia
muscle atrophy
axial hypotonia

Metabolic Features:
lactic acidosis

Abdomen Gastrointestinal:
poor feeding
impaired swallowing

Cardiovascular Heart:
cardiomyopathy (1 patient)

Neurologic Central Nervous System:
ataxia
hyperreflexia
hypertonia
absent speech
dysmetria
more
Laboratory Abnormalities:
hypoglycemia
increased serum lactate
defects in mitochondrial oxidative phosphorylation (oxphos) activity (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
aggressive behavior

Growth Other:
intrauterine growth retardation (iugr)


Clinical features from OMIM:

617710

Human phenotypes related to Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures:

32 (show all 25)
# Description HPO Frequency HPO Source Accession
1 nystagmus 32 HP:0000639
2 intellectual disability 32 HP:0001249
3 seizures 32 very rare (1%) HP:0001250
4 muscle weakness 32 HP:0001324
5 hyperreflexia 32 HP:0001347
6 global developmental delay 32 HP:0001263
7 optic atrophy 32 HP:0000648
8 spastic tetraplegia 32 HP:0002510
9 hypoglycemia 32 HP:0001943
10 skeletal muscle atrophy 32 HP:0003202
11 feeding difficulties 32 HP:0011968
12 absent speech 32 HP:0001344
13 dysmetria 32 HP:0001310
14 dystonia 32 HP:0001332
15 ventriculomegaly 32 HP:0002119
16 increased serum lactate 32 HP:0002151
17 amblyopia 32 HP:0000646
18 rod-cone dystrophy 32 very rare (1%) HP:0000510
19 cerebellar atrophy 32 HP:0001272
20 cerebral atrophy 32 HP:0002059
21 athetosis 32 HP:0002305
22 exotropia 32 HP:0000577
23 limb hypertonia 32 HP:0002509
24 muscular hypotonia of the trunk 32 HP:0008936
25 delayed myelination 32 HP:0012448

Drugs & Therapeutics for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

Search Clinical Trials , NIH Clinical Center for Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures

Genetic Tests for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

Genetic tests related to Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures:

# Genetic test Affiliating Genes
1 Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures 29 WARS2

Anatomical Context for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

MalaCards organs/tissues related to Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures:

41
Skeletal Muscle

Publications for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

Variations for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

UniProtKB/Swiss-Prot genetic disease variations for Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures:

75
# Symbol AA change Variation ID SNP ID
1 WARS2 p.Trp13Gly VAR_078435 rs139548132
2 WARS2 p.Gly45Val VAR_079734
3 WARS2 p.Val178Leu VAR_079737
4 WARS2 p.Lys313Met VAR_079738 rs145867327
5 WARS2 p.Val349Leu VAR_079739

ClinVar genetic disease variations for Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures:

6 (show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 WARS2 NM_015836.3(WARS2): c.325delA (p.Ser109Alafs) deletion Pathogenic GRCh38 Chromosome 1, 119076373: 119076373
2 WARS2 NM_015836.3(WARS2): c.325delA (p.Ser109Alafs) deletion Pathogenic GRCh37 Chromosome 1, 119618996: 119618996
3 WARS2 NM_015836.3(WARS2): c.37T> G (p.Trp13Gly) single nucleotide variant Pathogenic rs139548132 GRCh37 Chromosome 1, 119683231: 119683231
4 WARS2 NM_015836.3(WARS2): c.37T> G (p.Trp13Gly) single nucleotide variant Pathogenic rs139548132 GRCh38 Chromosome 1, 119140608: 119140608
5 WARS2 NM_015836.3(WARS2): c.298_300delCTT (p.Leu100del) deletion Uncertain significance rs772867219 GRCh38 Chromosome 1, 119076398: 119076400
6 WARS2 NM_015836.3(WARS2): c.298_300delCTT (p.Leu100del) deletion Uncertain significance rs772867219 GRCh37 Chromosome 1, 119619021: 119619023
7 WARS2 NM_015836.3(WARS2): c.938A> T (p.Lys313Met) single nucleotide variant Uncertain significance rs145867327 GRCh38 Chromosome 1, 119033056: 119033056
8 WARS2 NM_015836.3(WARS2): c.938A> T (p.Lys313Met) single nucleotide variant Uncertain significance rs145867327 GRCh37 Chromosome 1, 119575679: 119575679
9 WARS2 NM_015836.3(WARS2): c.797delC (p.Pro266Argfs) deletion Uncertain significance rs746478253 GRCh38 Chromosome 1, 119033197: 119033197
10 WARS2 NM_015836.3(WARS2): c.797delC (p.Pro266Argfs) deletion Uncertain significance rs746478253 GRCh37 Chromosome 1, 119575820: 119575820
11 WARS2 NM_015836.3(WARS2): c.134G> T (p.Gly45Val) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 119619187: 119619187
12 WARS2 NM_015836.3(WARS2): c.134G> T (p.Gly45Val) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 119076564: 119076564
13 WARS2 NM_015836.3(WARS2): c.532G> C (p.Val178Leu) single nucleotide variant Pathogenic rs912133959 GRCh37 Chromosome 1, 119576820: 119576820
14 WARS2 NM_015836.3(WARS2): c.532G> C (p.Val178Leu) single nucleotide variant Pathogenic rs912133959 GRCh38 Chromosome 1, 119034197: 119034197

Expression for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

Search GEO for disease gene expression data for Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures.

Pathways for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

GO Terms for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

Sources for Neurodevelopmental Disorder, Mitochondrial, with Abnormal...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....