NEMMLAS
MCID: NRD036
MIFTS: 22

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 58 76 30 6
Nemmlas 58 76

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype and severity
onset in early infancy


Classifications:



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

UniProtKB/Swiss-Prot : 76 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 seizures and rod-cone dystrophy

OMIM : 58 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...

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

33 (show all 25)
# Description HPO Frequency HPO Source Accession
1 seizures 33 very rare (1%) HP:0001250
2 rod-cone dystrophy 33 very rare (1%) HP:0000510
3 nystagmus 33 HP:0000639
4 intellectual disability 33 HP:0001249
5 muscle weakness 33 HP:0001324
6 hyperreflexia 33 HP:0001347
7 global developmental delay 33 HP:0001263
8 optic atrophy 33 HP:0000648
9 spastic tetraplegia 33 HP:0002510
10 hypoglycemia 33 HP:0001943
11 skeletal muscle atrophy 33 HP:0003202
12 feeding difficulties 33 HP:0011968
13 absent speech 33 HP:0001344
14 dysmetria 33 HP:0001310
15 dystonia 33 HP:0001332
16 ventriculomegaly 33 HP:0002119
17 increased serum lactate 33 HP:0002151
18 amblyopia 33 HP:0000646
19 cerebellar atrophy 33 HP:0001272
20 cerebral atrophy 33 HP:0002059
21 athetosis 33 HP:0002305
22 exotropia 33 HP:0000577
23 muscular hypotonia of the trunk 33 HP:0008936
24 limb hypertonia 33 HP:0002509
25 delayed myelination 33 HP:0012448

Symptoms via clinical synopsis from OMIM:

58
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

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 30 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:

42
Skeletal Muscle

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 Year
1
Biallelic variants in WARS2 encoding mitochondrial tryptophanyl-tRNA synthase in six individuals with mitochondrial encephalopathy. ( 28905505 )
2017
2
Mutations of the aminoacyl-tRNA-synthetases SARS and WARS2 are implicated in the etiology of autosomal recessive intellectual disability. ( 28236339 )
2017
3
Deficiency of WARS2, encoding mitochondrial tryptophanyl tRNA synthetase, causes severe infantile onset leukoencephalopathy. ( 28650581 )
2017

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:

76
# 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 rs117078031

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

6 (show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 WARS2 NM_201263.2(WARS2): c.325delA (p.Ser109Alafs) deletion Pathogenic rs1253426801 GRCh38 Chromosome 1, 119076373: 119076373
2 WARS2 NM_201263.2(WARS2): c.325delA (p.Ser109Alafs) deletion Pathogenic rs1253426801 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 rs1553241795 GRCh37 Chromosome 1, 119619187: 119619187
12 WARS2 NM_015836.3(WARS2): c.134G> T (p.Gly45Val) single nucleotide variant Pathogenic rs1553241795 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
15 WARS2 NM_015836.3(WARS2): c.317C> T (p.Pro106Leu) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 119619004: 119619004
16 WARS2 NM_015836.3(WARS2): c.317C> T (p.Pro106Leu) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 119076381: 119076381

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...

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