MLD
MCID: MTC067
MIFTS: 39

Metachromatic Leukodystrophy Due to Sap-B Deficiency (MLD) malady

Genetic diseases, Neuronal diseases, Eye diseases, Metabolic diseases, Rare diseases categories
Download this MalaCard

Summaries for Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section


Fully expand this MalaCard
MalaCards based summary: Metachromatic Leukodystrophy Due to Sap-B Deficiency, also known as metachromatic leukodystrophy, is related to leukodystrophy and metachromatic leukodystrophy, and has symptoms including genu recurvatum, peripheral neuropathy and nerve conduction abnormality. An important gene associated with Metachromatic Leukodystrophy Due to Sap-B Deficiency is PSAP (prosaposin), and among its related pathways are Lysosome and Sphingolipid metabolism. The compounds galactosylceramide and sulfatide have been mentioned in the context of this disorder. Affiliated tissues include eye, and related mouse phenotype hearing/vestibular/ear.

Descriptions from OMIM:46 156310,249900,250100

Aliases & Classifications for Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section
Sources:
46OMIM, 48Orphanet, 62UMLS, 63UMLS via Orphanet, 35MESH via Orphanet, 26ICD10 via Orphanet
See all sources

Metachromatic Leukodystrophy Due to Sap-B Deficiency, Aliases & Descriptions:

Name: Metachromatic Leukodystrophy Due to Sap-B Deficiency 46
Metachromatic Leukodystrophy 48 46
Arylsulfatase a Deficiency 48 62
 
Mld 48 62
Leukodystrophy, Metachromatic 62


Classifications:



Characteristics (Orphanet epidemiological data):

48
metachromatic leukodystrophy:
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000; Age of onset: Variable


External Ids:

UMLS via Orphanet63 C2713319, C0023522
MESH via Orphanet35 C538597, D007966
ICD10 via Orphanet26 E75.2

Related Diseases for Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section

Diseases related to Metachromatic Leukodystrophy Due to Sap-B Deficiency via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 57)
idRelated DiseaseScoreTop Affiliating Genes
1leukodystrophy32.4PSAP
2metachromatic leukodystrophy32.3PSAP, ARSA
3krabbe disease30.7ARSA, PSAP
4tay-sachs disease30.5PSAP, ARSA
5sphingolipidosis30.3ARSA, PSAP
6dementia10.6
7neuropathy10.6
8metachromatic leukodystrophy due to saposin b deficiency10.6
9cerebritis10.6
10adrenoleukodystrophy10.5
11neuronitis10.5
12peripheral neuropathy10.5
13fucosidosis10.4
14multiple sclerosis10.4
15schizophrenia10.4
16mucosulfatidosis10.4
17nervous system disease10.4
18neurologic diseases10.4
19metachromatic leukodystrophy, adult form10.4
20metachromatic leukodystrophy, late infantile form10.4
21metachromatic leukodystrophy, juvenile form10.4
22bipolar disorder10.2
23cerebellar ataxia10.2
24hematopoietic stem cell transplantation10.2
25hydrocephalus10.2
26mannosidosis10.2
27renal tubular acidosis10.2
28aspartylglucosaminuria10.2
29conduct disorder10.2
30cholelithiasis10.2
31sly syndrome10.2
32quadriplegia10.2
33spastic quadriplegia10.2
34cerebral lipidosis10.2
35central nervous system disease10.2
36cholecystitis10.2
37communicating hydrocephalus10.2
38dystonia10.2
39gangliosidosis10.2
40learning disability10.2
41polyneuropathy10.2
42thyroiditis10.2
43pseudoarylsulfatase a deficiency10.2
44ataxia10.2
45spasticity10.2
46lactic acidosis10.2
47pervasive developmental disorder10.2
48hypertension10.0
49pulmonary hypertension10.0
50turner syndrome10.0

Graphical network of the top 20 diseases related to Metachromatic Leukodystrophy Due to Sap-B Deficiency:



Diseases related to metachromatic leukodystrophy due to sap-b deficiency

Symptoms for Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section

Symptoms by clinical synopsis from OMIM:

156310

Clinical features from OMIM:

156310,249900,250100

Symptoms:

48 (show all 26)
  • genu recurvatum
  • peripheral neuropathy
  • nerve conduction abnormality
  • motor deficit/trouble
  • abnormal gait
  • ataxia/incoordination/trouble of the equilibrium
  • seizures/epilepsy/absences/spasms/status epilepticus
  • obnubilation/coma/lethargia/desorientation
  • speech troubles/aphasia/dysphasia/echolalia/mutism/logorrhea/dysprosodia
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • psychic/psychomotor regression/dementia/intellectual decline
  • psychic/behavioural troubles
  • muscle weakness/flaccidity
  • lipidosis/sulfatidosis
  • autosomal dominant inheritance
  • autosomal recessive inheritance
  • optic nerve anomaly/optic atrophy/anomaly of the papilla
  • transient amaurosis/acute visual trouble
  • nystagmus
  • hypotonia
  • hypertonia/spasticity/rigidity/stiffness
  • areflexia/hyporeflexia
  • hypereflexia
  • restricted joint mobility/joint stiffness/ankylosis
  • dolichocolon/megacolon/megadolichocolon/hirschsprung's disease
  • muscle anomalies

HPO human phenotypes related to Metachromatic Leukodystrophy Due to Sap-B Deficiency:

(show all 53)
id Description Frequency HPO Source Accession
1 behavioral abnormality hallmark (90%) HP:0000708
2 decreased nerve conduction velocity hallmark (90%) HP:0000762
3 seizures hallmark (90%) HP:0001250
4 gait disturbance hallmark (90%) HP:0001288
5 muscle weakness hallmark (90%) HP:0001324
6 neurological speech impairment hallmark (90%) HP:0002167
7 incoordination hallmark (90%) HP:0002311
8 developmental regression hallmark (90%) HP:0002376
9 genu recurvatum hallmark (90%) HP:0002816
10 reduced consciousness/confusion hallmark (90%) HP:0004372
11 peripheral neuropathy hallmark (90%) HP:0009830
12 cognitive impairment hallmark (90%) HP:0100543
13 nystagmus typical (50%) HP:0000639
14 optic atrophy typical (50%) HP:0000648
15 muscular hypotonia typical (50%) HP:0001252
16 hypertonia typical (50%) HP:0001276
17 reduced tendon reflexes typical (50%) HP:0001315
18 hyperreflexia typical (50%) HP:0001347
19 limitation of joint mobility typical (50%) HP:0001376
20 amaurosis fugax typical (50%) HP:0100576
21 aganglionic megacolon occasional (7.5%) HP:0002251
22 autosomal dominant inheritance HP:0000006
23 urinary urgency HP:0000012
24 urinary incontinence HP:0000020
25 abnormality of the endocrine system HP:0000818
26 abnormality of metabolism/homeostasis HP:0001939
27 hypotension HP:0002615
28 adult onset HP:0003581
29 metachromatic leukodystrophy variant HP:0006926
30 peripheral neuropathy HP:0009830
31 autosomal recessive inheritance HP:0000007
32 urinary incontinence HP:0000020
33 decreased nerve conduction velocity HP:0000762
34 seizures HP:0001250
35 muscular hypotonia HP:0001252
36 dysarthria HP:0001260
37 global developmental delay HP:0001263
38 hyporeflexia HP:0001265
39 mental deterioration HP:0001268
40 polyneuropathy HP:0001271
41 spastic tetraparesis HP:0001285
42 muscle weakness HP:0001324
43 muscle weakness HP:0001324
44 hyperreflexia HP:0001347
45 dysphagia HP:0002015
46 gait ataxia HP:0002066
47 loss of speech HP:0002371
48 developmental regression HP:0002376
49 abnormality of the periventricular white matter HP:0002518
50 babinski sign HP:0003487
51 variable expressivity HP:0003828
52 cns demyelination HP:0007305
53 peripheral demyelination HP:0011096

Drugs & Therapeutics for Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section

Drug clinical trials:

Search ClinicalTrials for Metachromatic Leukodystrophy Due to Sap-B Deficiency

Search NIH Clinical Center for Metachromatic Leukodystrophy Due to Sap-B Deficiency

Genetic Tests for Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section

Anatomical Context for Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section

MalaCards organs/tissues related to Metachromatic Leukodystrophy Due to Sap-B Deficiency:

32
Eye

Animal Models for Metachromatic Leukodystrophy Due to Sap-B Deficiency or affiliated genes

About this section

MGI Mouse Phenotypes related to Metachromatic Leukodystrophy Due to Sap-B Deficiency:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053779.1ARSA, PSAP

Publications for Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section

Variations for Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section

UniProtKB/Swiss-Prot genetic disease variations for Metachromatic Leukodystrophy Due to Sap-B Deficiency:

64
id Symbol AA change Variation ID SNP ID
1PSAPp.Thr217IleVAR_006943
2PSAPp.Cys241SerVAR_006944rs1130793
3PSAPp.Asn215HisVAR_031823
4PSAPp.Asn215LysVAR_031899

Clinvar genetic disease variations for Metachromatic Leukodystrophy Due to Sap-B Deficiency:

6 (show all 32)
id Gene Name Type Significance SNP ID Assembly Location
1PSAPNM_001042465.1(PSAP): c.650C> T (p.Thr217Ile)single nucleotide variantPathogenicrs121918103GRCh37Chr 10, 73587841: 73587841
2PSAPPSAP, IVS4AS, C-Asingle nucleotide variantPathogenic
3PSAPNM_001042465.1(PSAP): c.722G> C (p.Cys241Ser)single nucleotide variantPathogenicrs121918104GRCh37Chr 10, 73585649: 73585649
4PSAPPSAP, IVS5AS, G-T, -1single nucleotide variantPathogenic
5PSAPNM_001042465.1(PSAP): c.643A> C (p.Asn215His)single nucleotide variantPathogenicrs121918107GRCh37Chr 10, 73587848: 73587848
6PSAPPSAP, IVS5AS, A-G, -2single nucleotide variantPathogenic
7PSAPPSAP, 2-BP DEL, 828GAdeletionPathogenic
8ARSANM_000487.5(ARSA): c.1178C> G (p.Thr393Ser)single nucleotide variantPathogenicrs743616GRCh37Chr 22, 51064039: 51064039
9ARSANM_000487.5(ARSA): c.1407_1417delCGCAGCTGTGA (p.Ala470Leufs)deletionPathogenicrs80338823GRCh37Chr 22, 51063686: 51063696
10ARSANM_000487.5(ARSA): c.257G> A (p.Arg86Gln)single nucleotide variantPathogenicrs74315458GRCh37Chr 22, 51065802: 51065802
11ARSANM_000487.5(ARSA): c.769G> C (p.Asp257His)single nucleotide variantPathogenicrs80338819GRCh37Chr 22, 51065104: 51065104
12ARSANM_000487.5(ARSA): c.*96A> Gsingle nucleotide variantPathogenicrs6151429GRCh37Chr 22, 51063477: 51063477
13ARSANM_000487.5(ARSA): c.1055A> G (p.Asn352Ser)single nucleotide variantPathogenicrs2071421GRCh37Chr 22, 51064416: 51064416
14ARSANM_000487.5(ARSA): c.465+1G> Asingle nucleotide variantPathogenicrs80338815GRCh37Chr 22, 51065593: 51065593
15ARSANM_000487.5(ARSA): c.1283C> T (p.Pro428Leu)single nucleotide variantPathogenicrs28940893GRCh37Chr 22, 51063820: 51063820
16ARSANM_000487.5(ARSA): c.302G> A (p.Gly101Asp)single nucleotide variantPathogenicrs74315455GRCh37Chr 22, 51065757: 51065757
17ARSANM_000487.5(ARSA): c.293C> T (p.Ser98Phe)single nucleotide variantPathogenicrs74315456GRCh37Chr 22, 51065766: 51065766
18ARSANM_000487.5(ARSA): c.542T> G (p.Ile181Ser)single nucleotide variantPathogenicrs74315457GRCh37Chr 22, 51065404: 51065404
19ARSANM_000487.5(ARSA): c.1210+1G> Asingle nucleotide variantPathogenicrs80338820GRCh37Chr 22, 51064006: 51064006
20ARSANM_000487.5(ARSA): c.370G> A (p.Gly124Ser)single nucleotide variantPathogenicrs74315461GRCh37Chr 22, 51065689: 51065689
21ARSAARSA, 1-BP DEL, 297CdeletionPathogenic
22ARSANM_000487.5(ARSA): c.467G> A (p.Gly156Asp)single nucleotide variantPathogenicrs74315463GRCh37Chr 22, 51065479: 51065479
23ARSANM_000487.5(ARSA): c.506C> G (p.Pro169Arg)single nucleotide variantPathogenicrs74315465GRCh37Chr 22, 51065440: 51065440
24ARSANM_000487.5(ARSA): c.641C> T (p.Ala214Val)single nucleotide variantPathogenicrs74315467GRCh37Chr 22, 51065305: 51065305
25ARSANM_000487.5(ARSA): c.677C> T (p.Ala226Val)single nucleotide variantPathogenicrs74315468GRCh37Chr 22, 51065269: 51065269
26ARSANM_000487.5(ARSA): c.697C> A (p.Pro233Thr)single nucleotide variantPathogenicrs74315469GRCh37Chr 22, 51065176: 51065176
27ARSANM_000487.5(ARSA): c.736C> T (p.Arg246Cys)single nucleotide variantPathogenicrs74315470GRCh37Chr 22, 51065137: 51065137
28ARSANM_000487.5(ARSA): c.739G> A (p.Gly247Arg)single nucleotide variantPathogenicrs74315471GRCh37Chr 22, 51065134: 51065134
29ARSANM_000487.5(ARSA): c.868C> T (p.Arg290Cys)single nucleotide variantPathogenicrs74315473GRCh37Chr 22, 51064693: 51064693
30ARSANM_000487.5(ARSA): c.1174C> T (p.Arg392Trp)single nucleotide variantPathogenicrs74315480GRCh37Chr 22, 51064043: 51064043
31ARSAARSA, 3-BP DEL, PHE398DELdeletionPathogenic
32ARSANM_000487.5(ARSA): c.1232C> T (p.Thr411Ile)single nucleotide variantPathogenicrs74315481GRCh37Chr 22, 51063871: 51063871

Expression for genes affiliated with Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section
Expression patterns in normal tissues for genes affiliated with Metachromatic Leukodystrophy Due to Sap-B Deficiency

Search GEO for disease gene expression data for Metachromatic Leukodystrophy Due to Sap-B Deficiency.

Pathways for genes affiliated with Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section

Pathways related to Metachromatic Leukodystrophy Due to Sap-B Deficiency according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.1ARSA, PSAP
2
Show member pathways
9.1ARSA, PSAP

Compounds for genes affiliated with Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section
Sources:
44Novoseek, 24HMDB
See all sources

Compounds related to Metachromatic Leukodystrophy Due to Sap-B Deficiency according to GeneCards/GeneDecks:

(show all 13)
idCompoundScoreTop Affiliating Genes
1galactosylceramide449.4ARSA, PSAP
2sulfatide449.4ARSA, PSAP
3glycosphingolipid449.4ARSA, PSAP
43-O-Sulfogalactosylceramide (d18:1/24:0)249.4PSAP, ARSA
5ganglioside449.3ARSA, PSAP
6mannose 6-phosphate44 2410.3ARSA, PSAP
7sulfate44 2410.3PSAP, ARSA
8ceramide449.2ARSA, PSAP
9valine449.2ARSA, PSAP
10hydrogen44 2410.1PSAP, ARSA
11lipid449.1ARSA, PSAP
12oligonucleotide449.0ARSA, PSAP
13cysteine448.8ARSA, PSAP

GO Terms for genes affiliated with Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section

Cellular components related to Metachromatic Leukodystrophy Due to Sap-B Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1extracellular spaceGO:0056159.1ARSA, PSAP
2lysosomal lumenGO:0432028.8ARSA, PSAP

Biological processes related to Metachromatic Leukodystrophy Due to Sap-B Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1sphingolipid metabolic processGO:0066659.1ARSA, PSAP
2glycosphingolipid metabolic processGO:0066878.8ARSA, PSAP

Products for genes affiliated with Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section
  • Antibodies
  • Proteins
  • Lysates

Sources for Metachromatic Leukodystrophy Due to Sap-B Deficiency

About this section
3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet