NEMMLAS
MCID: NRD036
MIFTS: 32

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

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare 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 72 29 6
Nemmlas 57 72
Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with/without Seizures 39
Wars2-Related Combined Oxidative Phosphorylation Defect 58
Mitochondrial Tryptophanyl-Trna Synthetase Deficiency 58

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype and severity
onset in early infancy


HPO:

31
neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


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

UniProtKB/Swiss-Prot : 72 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, also known as nemmlas, is related to lactic acidosis and seizure disorder. 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 liver, and related phenotypes are global developmental delay and hyperreflexia

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) (Updated 20-May-2021)

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

Diseases related to Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 lactic acidosis 10.6
2 seizure disorder 10.6
3 ataxia and polyneuropathy, adult-onset 10.5
4 parkinsonism 10.5
5 alacrima, achalasia, and mental retardation syndrome 10.3
6 cerebral palsy 10.3
7 liver disease 10.3
8 encephalopathy 10.3
9 acute liver failure 10.3

Graphical network of the top 20 diseases related to Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures:



Diseases related to Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis, with or Without Seizures

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

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

58 31 (show top 50) (show all 64)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
2 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
3 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001511
4 increased serum lactate 58 31 frequent (33%) Frequent (79-30%) HP:0002151
5 intellectual disability, moderate 58 31 frequent (33%) Frequent (79-30%) HP:0002342
6 lactic acidosis 58 31 frequent (33%) Frequent (79-30%) HP:0003128
7 cerebellar atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0001272
8 abnormal enzyme/coenzyme activity 58 31 frequent (33%) Frequent (79-30%) HP:0012379
9 cerebral atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002059
10 aggressive behavior 58 31 frequent (33%) Frequent (79-30%) HP:0000718
11 abnormality of the periventricular white matter 58 31 frequent (33%) Frequent (79-30%) HP:0002518
12 limb dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0002451
13 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
14 generalized amyotrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003700
15 cerebral white matter hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0012430
16 limb hypertonia 58 31 frequent (33%) Frequent (79-30%) HP:0002509
17 delayed myelination 58 31 frequent (33%) Frequent (79-30%) HP:0012448
18 infantile axial hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0009062
19 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
20 tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0001337
21 dysphagia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002015
22 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
23 hypertelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000316
24 wide nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0000431
25 abnormal facial shape 58 31 occasional (7.5%) Occasional (29-5%) HP:0001999
26 spastic tetraplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002510
27 absent speech 58 31 occasional (7.5%) Occasional (29-5%) HP:0001344
28 low-set ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000369
29 thrombocytopenia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001873
30 thin upper lip vermilion 58 31 occasional (7.5%) Occasional (29-5%) HP:0000219
31 amblyopia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000646
32 dysmetria 58 31 occasional (7.5%) Occasional (29-5%) HP:0001310
33 neonatal hypoglycemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001998
34 rod-cone dystrophy 58 31 very rare (1%) Occasional (29-5%) HP:0000510
35 poor head control 58 31 occasional (7.5%) Occasional (29-5%) HP:0002421
36 cardiomyopathy 58 31 very rare (1%) Occasional (29-5%) HP:0001638
37 intellectual disability, profound 58 31 occasional (7.5%) Occasional (29-5%) HP:0002187
38 cerebellar vermis hypoplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001320
39 athetosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002305
40 exotropia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000577
41 widened subarachnoid space 58 31 occasional (7.5%) Occasional (29-5%) HP:0012704
42 positional foot deformity 58 31 occasional (7.5%) Occasional (29-5%) HP:0005656
43 hypoplasia of the brainstem 58 31 occasional (7.5%) Occasional (29-5%) HP:0002365
44 difficulty standing 58 31 occasional (7.5%) Occasional (29-5%) HP:0003698
45 impaired smooth pursuit 58 31 occasional (7.5%) Occasional (29-5%) HP:0007772
46 dilation of lateral ventricles 58 31 occasional (7.5%) Occasional (29-5%) HP:0006956
47 dilated fourth ventricle 58 31 occasional (7.5%) Occasional (29-5%) HP:0002198
48 multifocal seizures 58 31 occasional (7.5%) Occasional (29-5%) HP:0031165
49 seizure 31 very rare (1%) HP:0001250
50 intellectual disability 58 31 Very frequent (99-80%) HP:0001249

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
hyperreflexia
ataxia
hypertonia
absent speech
dysmetria
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)

Head And Neck Eyes:
nystagmus
optic atrophy
strabismus
amblyopia
exotropia
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 (Updated 20-May-2021)

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:

40
Skeletal Muscle, Liver

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

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

# Title Authors PMID Year
1
Biallelic variants in WARS2 encoding mitochondrial tryptophanyl-tRNA synthase in six individuals with mitochondrial encephalopathy. 6 57
28905505 2017
2
Deficiency of WARS2, encoding mitochondrial tryptophanyl tRNA synthetase, causes severe infantile onset leukoencephalopathy. 57 6
28650581 2017
3
Mutations of the aminoacyl-tRNA-synthetases SARS and WARS2 are implicated in the etiology of autosomal recessive intellectual disability. 6 57
28236339 2017
4
NEMMLAS Due to Biallelic WARS2 Variants. 61
31617452 2020
5
Expanding the Phenotype: Neurodevelopmental Disorder, Mitochondrial, With Abnormal Movements and Lactic Acidosis, With or Without Seizures (NEMMLAS) Due to WARS2 Biallelic Variants, Encoding Mitochondrial Tryptophanyl-tRNA Synthase. 61
31684799 2020
6
Expanding the Phenotype: Neurodevelopmental Disorder, Mitochondrial, With Abnormal Movements and Lactic Acidosis, With or Without Seizures (NEMMLAS) due to WARS2 Biallelic Variants, Encoding Mitochondrial Tryptophanyl-tRNA Synthase. 61
31282308 2019

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

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

6 (show all 17)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 WARS2 NM_015836.4(WARS2):c.622G>T (p.Glu208Ter) SNV Pathogenic 976753 GRCh37: 1:119576730-119576730
GRCh38: 1:119034107-119034107
2 WARS2 and overlap with 1 gene(s) NM_015836.4(WARS2):c.91-8725_349-3571del Deletion Pathogenic 976754 GRCh37: 1:119591856-119627955
GRCh38: 1:119049233-119085332
3 WARS2 NM_015836.3(WARS2):c.134G>T (p.Gly45Val) SNV Pathogenic 440919 rs1553241795 GRCh37: 1:119619187-119619187
GRCh38: 1:119076564-119076564
4 WARS2 NM_201263.2(WARS2):c.295_297CTT[1] (p.Leu100del) Microsatellite Pathogenic 440916 rs772867219 GRCh37: 1:119619021-119619023
GRCh38: 1:119076398-119076400
5 WARS2 NM_015836.3(WARS2):c.325del (p.Ser109fs) Deletion Pathogenic 440914 rs1253426801 GRCh37: 1:119618996-119618996
GRCh38: 1:119076373-119076373
6 WARS2 NM_015836.3(WARS2):c.532G>C (p.Val178Leu) SNV Pathogenic 440920 rs912133959 GRCh37: 1:119576820-119576820
GRCh38: 1:119034197-119034197
7 WARS2 NM_015836.3(WARS2):c.938A>T (p.Lys313Met) SNV Pathogenic 440917 rs145867327 GRCh37: 1:119575679-119575679
GRCh38: 1:119033056-119033056
8 WARS2 NM_201263.2(WARS2):c.*163del Deletion Pathogenic 440918 rs746478253 GRCh37: 1:119575820-119575820
GRCh38: 1:119033197-119033197
9 WARS2 NM_015836.3(WARS2):c.149G>A (p.Gly50Asp) SNV Likely pathogenic 807717 rs1571323203 GRCh37: 1:119619172-119619172
GRCh38: 1:119076549-119076549
10 WARS2-AS1 , WARS2 NM_015836.3(WARS2):c.37T>G (p.Trp13Gly) SNV Conflicting interpretations of pathogenicity 440915 rs139548132 GRCh37: 1:119683231-119683231
GRCh38: 1:119140608-119140608
11 WARS2 NM_015836.3(WARS2):c.317C>T (p.Pro106Leu) SNV Uncertain significance 592126 rs753188889 GRCh37: 1:119619004-119619004
GRCh38: 1:119076381-119076381
12 WARS2 NM_015836.4(WARS2):c.683C>G (p.Ser228Trp) SNV Uncertain significance 986388 GRCh37: 1:119575934-119575934
GRCh38: 1:119033311-119033311
13 WARS2 NM_015836.4(WARS2):c.1016C>T (p.Ser339Leu) SNV Uncertain significance 1028002 GRCh37: 1:119575601-119575601
GRCh38: 1:119032978-119032978
14 WARS2 NM_015836.4(WARS2):c.348+3C>T SNV Uncertain significance 1029412 GRCh37: 1:119618970-119618970
GRCh38: 1:119076347-119076347
15 WARS2 NM_015836.4(WARS2):c.404G>A (p.Arg135Gln) SNV Uncertain significance 1029413 GRCh37: 1:119588230-119588230
GRCh38: 1:119045607-119045607
16 WARS2 NM_015836.4(WARS2):c.899C>T (p.Ala300Val) SNV Uncertain significance 1029414 GRCh37: 1:119575718-119575718
GRCh38: 1:119033095-119033095
17 WARS2 NM_015836.4(WARS2):c.487C>T (p.Leu163Phe) SNV Uncertain significance 1031940 GRCh37: 1:119584915-119584915
GRCh38: 1:119042292-119042292

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

72
# Symbol AA change Variation ID SNP ID
1 WARS2 p.Trp13Gly VAR_078435 rs139548132
2 WARS2 p.Gly45Val VAR_079734 rs155324179
3 WARS2 p.Val178Leu VAR_079737 rs912133959
4 WARS2 p.Lys313Met VAR_079738 rs145867327
5 WARS2 p.Val349Leu VAR_079739 rs117078031

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 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....