MCID: LKN026
MIFTS: 32

Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation

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

Aliases & Classifications for Leukoencephalopathy with Brainstem and Spinal Cord Involvement...

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

Name: Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation 57 25 75 29 6 73
Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation 57 24 53 37 29 13 6
Lbsl 57 24 53 25 59 75
Mitochondrial Aspartyl-Trna Synthetase Deficiency 57 24 53 25
Leukoencephalopathy with Brain Stem and Spinal Cord Involvement-Lactate Elevation Syndrome 53 59
Leukoencephalopathy with Brain Stem and Spinal Cord Involvement-High Lactate Syndrome 53 59
Leukoencephalopathy with Brain Stem and Spinal Cord Involvement - Lactate Elevation 53
Leukoencephalopathy with Brain Stem and Spinal Cord Involvement - High Lactate 53
Leukoencephalopathy, Brain Stem and Spinal Cord Involvement, Lactate Elevation 40

Characteristics:

Orphanet epidemiological data:

59
leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
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 brainstem and spinal cord involvement and lactate elevation:
Onset and clinical course variable expressivity slow progression
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Leukoencephalopathy with Brainstem and Spinal Cord Involvement...

NIH Rare Diseases : 53 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.

MalaCards based summary : Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation, also known as leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, is related to spastic paraparesis and spasticity, and has symptoms including ataxia, muscle spasticity and tremor. An important gene associated with Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation is DARS2 (Aspartyl-TRNA Synthetase 2, Mitochondrial), and among its related pathways/superpathways is Aminoacyl-tRNA biosynthesis. Affiliated tissues include spinal cord, brain and testes, and related phenotypes are nystagmus and ataxia

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 : 57 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 : 75 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 Brainstem and Spinal Cord Involvement...

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

# Related Disease Score Top Affiliating Genes
1 spastic paraparesis 10.1
2 spasticity 10.1

Symptoms & Phenotypes for Leukoencephalopathy with Brainstem and Spinal Cord Involvement...

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus

Muscle Soft Tissue:
muscle weakness
muscle atrophy

Skeletal:
joint contractures (with age)

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


Clinical features from OMIM:

611105

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

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

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


ataxia, muscle spasticity, tremor, muscle weakness

Drugs & Therapeutics for Leukoencephalopathy with Brainstem and Spinal Cord Involvement...

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

Genetic Tests for Leukoencephalopathy with Brainstem and Spinal Cord Involvement...

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

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

Anatomical Context for Leukoencephalopathy with Brainstem and Spinal Cord Involvement...

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

41
Spinal Cord, Brain, Testes, Skeletal Muscle, Cerebellum

Publications for Leukoencephalopathy with Brainstem and Spinal Cord Involvement...

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

# Title Authors Year
1
Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) with a novel DARS2 mutation and isolated progressive spastic paraparesis. ( 28017220 )
2017
2
Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: clinical and genetic characterization and target for therapy. ( 24566671 )
2014
3
Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL): assessment of the involved white matter tracts by MRI. ( 24558666 )
2014
4
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA. ( 22023289 )
2012
5
[Clinical and molecular genetic diagnosis of leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation in children]. ( 19770827 )
2009
6
Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. ( 17384640 )
2007
7
Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation ( 20506600 )
1993

Variations for Leukoencephalopathy with Brainstem and Spinal Cord Involvement...

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

75 (show all 11)
# 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 Brainstem and Spinal Cord Involvement and Lactate Elevation:

6
(show top 50) (show all 67)
# 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.228-21_228-20delTTinsC indel Pathogenic rs367543010 GRCh38 Chromosome 1, 173828312: 173828313
3 DARS2 NM_018122.4(DARS2): c.1876C> G (p.Leu626Val) single nucleotide variant Pathogenic rs121918205 GRCh37 Chromosome 1, 173826781: 173826781
4 DARS2 NM_018122.4(DARS2): c.1876C> G (p.Leu626Val) single nucleotide variant Pathogenic rs121918205 GRCh38 Chromosome 1, 173857643: 173857643
5 DARS2 NM_018122.4(DARS2): c.787C> T (p.Arg263Ter) single nucleotide variant Pathogenic rs121918206 GRCh37 Chromosome 1, 173807344: 173807344
6 DARS2 NM_018122.4(DARS2): c.787C> T (p.Arg263Ter) single nucleotide variant Pathogenic rs121918206 GRCh38 Chromosome 1, 173838206: 173838206
7 DARS2 NM_018122.4(DARS2): c.788G> A (p.Arg263Gln) single nucleotide variant Pathogenic rs121918207 GRCh37 Chromosome 1, 173807345: 173807345
8 DARS2 NM_018122.4(DARS2): c.788G> A (p.Arg263Gln) single nucleotide variant Pathogenic rs121918207 GRCh38 Chromosome 1, 173838207: 173838207
9 DARS2 NM_018122.4(DARS2): c.455G> T (p.Cys152Phe) single nucleotide variant Pathogenic rs121918208 GRCh37 Chromosome 1, 173800731: 173800731
10 DARS2 NM_018122.4(DARS2): c.455G> T (p.Cys152Phe) single nucleotide variant Pathogenic rs121918208 GRCh38 Chromosome 1, 173831593: 173831593
11 DARS2 NM_018122.4(DARS2): c.492+2T> C single nucleotide variant Pathogenic rs142433332 GRCh37 Chromosome 1, 173800770: 173800770
12 DARS2 NM_018122.4(DARS2): c.492+2T> C single nucleotide variant Pathogenic rs142433332 GRCh38 Chromosome 1, 173831632: 173831632
13 DARS2 NM_018122.4(DARS2): c.133A> G (p.Ser45Gly) single nucleotide variant Pathogenic rs121918209 GRCh37 Chromosome 1, 173795830: 173795830
14 DARS2 NM_018122.4(DARS2): c.133A> G (p.Ser45Gly) single nucleotide variant Pathogenic rs121918209 GRCh38 Chromosome 1, 173826692: 173826692
15 DARS2 NM_018122.4(DARS2): c.536G> A (p.Arg179His) single nucleotide variant Pathogenic rs121918210 GRCh37 Chromosome 1, 173802557: 173802557
16 DARS2 NM_018122.4(DARS2): c.536G> A (p.Arg179His) single nucleotide variant Pathogenic rs121918210 GRCh38 Chromosome 1, 173833419: 173833419
17 DARS2 NM_018122.4(DARS2): c.1273G> T (p.Glu425Ter) single nucleotide variant Pathogenic rs121918211 GRCh37 Chromosome 1, 173819546: 173819546
18 DARS2 NM_018122.4(DARS2): c.1273G> T (p.Glu425Ter) single nucleotide variant Pathogenic rs121918211 GRCh38 Chromosome 1, 173850408: 173850408
19 DARS2 NM_018122.4(DARS2): c.1837C> T (p.Leu613Phe) single nucleotide variant Pathogenic rs121918212 GRCh37 Chromosome 1, 173826742: 173826742
20 DARS2 NM_018122.4(DARS2): c.1837C> T (p.Leu613Phe) single nucleotide variant Pathogenic rs121918212 GRCh38 Chromosome 1, 173857604: 173857604
21 DARS2 NM_018122.4(DARS2): c.1877T> A (p.Leu626Gln) single nucleotide variant Pathogenic rs121918213 GRCh37 Chromosome 1, 173826782: 173826782
22 DARS2 NM_018122.4(DARS2): c.1877T> A (p.Leu626Gln) single nucleotide variant Pathogenic rs121918213 GRCh38 Chromosome 1, 173857644: 173857644
23 DARS2 DARS2, IVS2, T-A, -22 single nucleotide variant Pathogenic
24 DARS2 NM_018122.4(DARS2): c.1825C> T (p.Arg609Trp) single nucleotide variant Pathogenic rs200670286 GRCh37 Chromosome 1, 173826730: 173826730
25 DARS2 NM_018122.4(DARS2): c.1825C> T (p.Arg609Trp) single nucleotide variant Pathogenic rs200670286 GRCh38 Chromosome 1, 173857592: 173857592
26 DARS2 NM_018122.4(DARS2): c.128-5T> A single nucleotide variant Likely benign rs200078808 GRCh38 Chromosome 1, 173826682: 173826682
27 DARS2 NM_018122.4(DARS2): c.128-5T> A single nucleotide variant Likely benign rs200078808 GRCh37 Chromosome 1, 173795820: 173795820
28 DARS2 NM_018122.4(DARS2): c.1715A> C (p.Asp572Ala) single nucleotide variant Uncertain significance rs886045590 GRCh37 Chromosome 1, 173825844: 173825844
29 DARS2 NM_018122.4(DARS2): c.1715A> C (p.Asp572Ala) single nucleotide variant Uncertain significance rs886045590 GRCh38 Chromosome 1, 173856706: 173856706
30 DARS2 NM_018122.4(DARS2): c.1750+11T> C single nucleotide variant Uncertain significance rs535671373 GRCh37 Chromosome 1, 173825890: 173825890
31 DARS2 NM_018122.4(DARS2): c.1750+11T> C single nucleotide variant Uncertain significance rs535671373 GRCh38 Chromosome 1, 173856752: 173856752
32 DARS2 NM_018122.4(DARS2): c.1758C> T (p.Asp586=) single nucleotide variant Conflicting interpretations of pathogenicity rs371048800 GRCh37 Chromosome 1, 173826663: 173826663
33 DARS2 NM_018122.4(DARS2): c.1758C> T (p.Asp586=) single nucleotide variant Conflicting interpretations of pathogenicity rs371048800 GRCh38 Chromosome 1, 173857525: 173857525
34 DARS2 NM_018122.4(DARS2): c.1804A> G (p.Ile602Val) single nucleotide variant Uncertain significance rs779305793 GRCh37 Chromosome 1, 173826709: 173826709
35 DARS2 NM_018122.4(DARS2): c.1804A> G (p.Ile602Val) single nucleotide variant Uncertain significance rs779305793 GRCh38 Chromosome 1, 173857571: 173857571
36 DARS2 NM_018122.4(DARS2): c.567G> A (p.Leu189=) single nucleotide variant Conflicting interpretations of pathogenicity rs547708828 GRCh38 Chromosome 1, 173833450: 173833450
37 DARS2 NM_018122.4(DARS2): c.567G> A (p.Leu189=) single nucleotide variant Conflicting interpretations of pathogenicity rs547708828 GRCh37 Chromosome 1, 173802588: 173802588
38 DARS2 NM_018122.4(DARS2): c.*653T> G single nucleotide variant Uncertain significance rs886045593 GRCh37 Chromosome 1, 173827496: 173827496
39 DARS2 NM_018122.4(DARS2): c.*653T> G single nucleotide variant Uncertain significance rs886045593 GRCh38 Chromosome 1, 173858358: 173858358
40 DARS2 NM_018122.4(DARS2): c.-522G> C single nucleotide variant Uncertain significance rs886045585 GRCh38 Chromosome 1, 173824708: 173824708
41 DARS2 NM_018122.4(DARS2): c.-522G> C single nucleotide variant Uncertain significance rs886045585 GRCh37 Chromosome 1, 173793846: 173793846
42 DARS2 NM_018122.4(DARS2): c.1558A> C (p.Lys520Gln) single nucleotide variant Uncertain significance rs201876507 GRCh37 Chromosome 1, 173822700: 173822700
43 DARS2 NM_018122.4(DARS2): c.1558A> C (p.Lys520Gln) single nucleotide variant Uncertain significance rs201876507 GRCh38 Chromosome 1, 173853562: 173853562
44 DARS2 NM_018122.4(DARS2): c.*168C> T single nucleotide variant Uncertain significance rs550840346 GRCh37 Chromosome 1, 173827011: 173827011
45 DARS2 NM_018122.4(DARS2): c.*168C> T single nucleotide variant Uncertain significance rs550840346 GRCh38 Chromosome 1, 173857873: 173857873
46 DARS2 NM_018122.4(DARS2): c.*642C> A single nucleotide variant Likely benign rs140743566 GRCh37 Chromosome 1, 173827485: 173827485
47 DARS2 NM_018122.4(DARS2): c.*642C> A single nucleotide variant Likely benign rs140743566 GRCh38 Chromosome 1, 173858347: 173858347
48 DARS2 NM_018122.4(DARS2): c.-533G> A single nucleotide variant Uncertain significance rs533128814 GRCh38 Chromosome 1, 173824697: 173824697
49 DARS2 NM_018122.4(DARS2): c.-533G> A single nucleotide variant Uncertain significance rs533128814 GRCh37 Chromosome 1, 173793835: 173793835
50 DARS2 NM_018122.4(DARS2): c.261T> C (p.Asp87=) single nucleotide variant Uncertain significance rs182096636 GRCh38 Chromosome 1, 173828366: 173828366

Expression for Leukoencephalopathy with Brainstem and Spinal Cord Involvement...

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

Pathways for Leukoencephalopathy with Brainstem and Spinal Cord Involvement...

Pathways related to Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation according to KEGG:

37
# Name Kegg Source Accession
1 Aminoacyl-tRNA biosynthesis hsa00970

GO Terms for Leukoencephalopathy with Brainstem and Spinal Cord Involvement...

Sources for Leukoencephalopathy with Brainstem and Spinal Cord Involvement...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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30 HGMD
31 HMDB
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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
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