MCID: LKN003
MIFTS: 31

Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

MalaCards integrated aliases for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation:

Name: Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation 54 23 50 24 29 13
Lbsl 23 50 24 25 56 71
Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation 25 71 29 69
Mitochondrial Aspartyl-Trna Synthetase Deficiency 23 50 24 25
Leukoencephalopathy with Brain Stem and Spinal Cord Involvement-Lactate Elevation Syndrome 50 56
Leukoencephalopathy with Brain Stem and Spinal Cord Involvement-High Lactate Syndrome 50 56
Leukoencephalopathy with Brain Stem and Spinal Cord Involvement - Lactate Elevation 50
Leukoencephalopathy with Brain Stem and Spinal Cord Involvement - High Lactate 50

Characteristics:

Orphanet epidemiological data:

56
leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
slowly progressive
onset between age 2 and 15 years
one patient with episodic ataxia and later onset has been reported (as of june 2010)


HPO:

32
leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation:
Onset and clinical course variable expressivity slow progression
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

NIH Rare Diseases : 50 leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (lbsl) is a rare neurological disease characterized by slowly progressive cerebellar ataxia (lack of control of the movements) and spasticity with dorsal column dysfunction (decreased position and vibration sense) in most patients. the disease involves the legs more than the arms. it usually starts in childhood or adolescence, but in some cases not until adulthood. difficulty speaking develops over time. other symptoms may include: epilepsy; learning problems; cognitive decline; and reduced consciousness, neurologic deterioration, and fever following minor head trauma. many affected individuals become wheelchair dependent in their teens or twenties. the earlier the onset the more severe the disease is. the diagnosis is made in persons who had the characteristic abnormalities observed on brain and spinal cord mri scans and with the genetic test identifiying the dars2 gene alteration (mutation). there is still no cure and treatment is supportive and includes physical therapy and rehabilitation to improve movement function, and the following as needed: antiepileptic drugs, special education and speech therapy. last updated: 6/24/2015

MalaCards based summary : Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation, also known as lbsl, is related to spastic paraparesis and spasticity, and has symptoms including nystagmus, dysarthria and ataxia. An important gene associated with Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation is DARS2 (Aspartyl-TRNA Synthetase 2, Mitochondrial). Affiliated tissues include spinal cord, brain and testes.

Genetics Home Reference : 25 Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (commonly referred to as LBSL) is a progressive disorder that affects the brain and spinal cord. Leukoencephalopathy refers to abnormalities in the white matter of the brain, which is tissue containing nerve cell fibers (axons) that transmit nerve impulses.

OMIM : 54
Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is defined on the basis of a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy (Scheper et al., 2007). Affected individuals develop slowly progressive cerebellar ataxia, spasticity, and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline. (611105)

UniProtKB/Swiss-Prot : 71 Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: Autosomal recessive disease and is defined on the basis of a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. Affected individuals develop slowly progressive cerebellar ataxia, spasticity, and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline.

GeneReviews: NBK43417

Related Diseases for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

Diseases related to Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 spastic paraparesis 9.8
2 spasticity 9.8

Symptoms & Phenotypes for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
delayed motor development
ataxia
tremor
hyperreflexia
spasticity
more
Neurologic- Peripheral Nervous System:
hyporeflexia
peripheral axonal neuropathy
decreased proprioception and vibration sense

Skeletal:
joint contractures (with age)

Head And Neck- Eyes:
nystagmus

Muscle Soft Tissue:
muscle weakness
muscle atrophy


Clinical features from OMIM:

611105

Human phenotypes related to Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation:

32 (show all 15)
id Description HPO Frequency HPO Source Accession
1 nystagmus 32 HP:0000639
2 dysarthria 32 occasional (7.5%) HP:0001260
3 ataxia 32 HP:0001251
4 tremor 32 HP:0001337
5 hyporeflexia 32 HP:0001265
6 hyperreflexia 32 HP:0001347
7 spasticity 32 HP:0001257
8 cognitive impairment 32 occasional (7.5%) HP:0100543
9 muscle weakness 32 HP:0001324
10 motor delay 32 HP:0001270
11 leukoencephalopathy 32 HP:0002352
12 peripheral axonal neuropathy 32 HP:0003477
13 babinski sign 32 HP:0003487
14 flexion contracture 32 HP:0001371
15 skeletal muscle atrophy 32 HP:0003202

UMLS symptoms related to Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation:


ataxia, muscle spasticity, tremor, muscle weakness

Drugs & Therapeutics for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

Search Clinical Trials , NIH Clinical Center for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation

Genetic Tests for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

Genetic tests related to Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation:

id Genetic test Affiliating Genes
1 Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation 29
2 Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation 29 24 DARS2

Anatomical Context for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

MalaCards organs/tissues related to Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation:

39
Spinal Cord, Brain, Testes, Skeletal Muscle, Cerebellum

Publications for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

Articles related to Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation:

id Title Authors Year
1
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA. ( 22023289 )
2012
2
Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. ( 17384640 )
2007
3
Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation ( 20506600 )
1993

Variations for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

UniProtKB/Swiss-Prot genetic disease variations for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation:

71 (show all 11)
id Symbol AA change Variation ID SNP ID
1 DARS2 p.Ser45Gly VAR_037015 rs121918209
2 DARS2 p.Cys152Phe VAR_037016 rs121918208
3 DARS2 p.Arg179His VAR_037017 rs121918210
4 DARS2 p.Gln184Lys VAR_037018
5 DARS2 p.Gln248Lys VAR_037019 rs772489337
6 DARS2 p.Arg263Gln VAR_037020 rs121918207
7 DARS2 p.Asp560Val VAR_037021 rs770525873
8 DARS2 p.Leu613Phe VAR_037022 rs121918212
9 DARS2 p.Leu626Gln VAR_037023 rs121918213
10 DARS2 p.Leu626Val VAR_037024 rs121918205
11 DARS2 p.Tyr629Cys VAR_037025 rs761675657

ClinVar genetic disease variations for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation:

6 (show all 13)
id Gene Variation Type Significance SNP ID Assembly Location
1 DARS2 NM_018122.4(DARS2): c.228-21_228-20delTTinsC indel Pathogenic rs367543010 GRCh37 Chromosome 1, 173797450: 173797451
2 DARS2 NM_018122.4(DARS2): c.1876C> G (p.Leu626Val) single nucleotide variant Pathogenic rs121918205 GRCh37 Chromosome 1, 173826781: 173826781
3 DARS2 NM_018122.4(DARS2): c.787C> T (p.Arg263Ter) single nucleotide variant Pathogenic rs121918206 GRCh37 Chromosome 1, 173807344: 173807344
4 DARS2 NM_018122.4(DARS2): c.788G> A (p.Arg263Gln) single nucleotide variant Pathogenic rs121918207 GRCh37 Chromosome 1, 173807345: 173807345
5 DARS2 NM_018122.4(DARS2): c.455G> T (p.Cys152Phe) single nucleotide variant Pathogenic rs121918208 GRCh37 Chromosome 1, 173800731: 173800731
6 DARS2 NM_018122.4(DARS2): c.492+2T> C single nucleotide variant Pathogenic rs142433332 GRCh37 Chromosome 1, 173800770: 173800770
7 DARS2 NM_018122.4(DARS2): c.133A> G (p.Ser45Gly) single nucleotide variant Pathogenic rs121918209 GRCh37 Chromosome 1, 173795830: 173795830
8 DARS2 NM_018122.4(DARS2): c.536G> A (p.Arg179His) single nucleotide variant Pathogenic rs121918210 GRCh37 Chromosome 1, 173802557: 173802557
9 DARS2 NM_018122.4(DARS2): c.1273G> T (p.Glu425Ter) single nucleotide variant Pathogenic rs121918211 GRCh37 Chromosome 1, 173819546: 173819546
10 DARS2 NM_018122.4(DARS2): c.1837C> T (p.Leu613Phe) single nucleotide variant Pathogenic rs121918212 GRCh37 Chromosome 1, 173826742: 173826742
11 DARS2 NM_018122.4(DARS2): c.1877T> A (p.Leu626Gln) single nucleotide variant Pathogenic rs121918213 GRCh37 Chromosome 1, 173826782: 173826782
12 DARS2 DARS2, IVS2, T-A, -22 single nucleotide variant Pathogenic
13 DARS2 NM_018122.4(DARS2): c.1825C> T (p.Arg609Trp) single nucleotide variant Pathogenic rs200670286 GRCh37 Chromosome 1, 173826730: 173826730

Expression for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

Search GEO for disease gene expression data for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation.

Pathways for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

GO Terms for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

Sources for Leukoencephalopathy with Brain Stem and Spinal Cord Involvement...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
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48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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