MLD-SAPB
MCID: MTC019
MIFTS: 32

Metachromatic Leukodystrophy Due to Saposin B Deficiency (MLD-SAPB)

Categories: Genetic diseases, Rare diseases

Aliases & Classifications for Metachromatic Leukodystrophy Due to Saposin B Deficiency

MalaCards integrated aliases for Metachromatic Leukodystrophy Due to Saposin B Deficiency:

Name: Metachromatic Leukodystrophy Due to Saposin B Deficiency 57 20 6 70
Metachromatic Leukodystrophy Due to Cerebroside Sulfatase Activator Deficiency 57 20 72
Metachromatic Leukodystrophy Due to Sap-B Deficiency 57 13
Saposin B Deficiency 57 72
Metachromatic Leukodystrophy Due to Saposin-B Deficiency 72
Activator Deficiency 72
Mld-Sapb 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
variable age at onset (infant to adult)
disease course depends on age at onset


HPO:

31
metachromatic leukodystrophy due to saposin b deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:



Summaries for Metachromatic Leukodystrophy Due to Saposin B Deficiency

UniProtKB/Swiss-Prot : 72 Metachromatic leukodystrophy due to saposin-B deficiency: An atypical form of metachromatic leukodystrophy. It is characterized by tissue accumulation of cerebroside-3-sulfate, demyelination, periventricular white matter abnormalities, peripheral neuropathy. Additional neurological features include dysarthria, ataxic gait, psychomotor regression, seizures, cognitive decline and spastic quadriparesis.

MalaCards based summary : Metachromatic Leukodystrophy Due to Saposin B Deficiency, also known as metachromatic leukodystrophy due to cerebroside sulfatase activator deficiency, is related to gm2-gangliosidosis, ab variant and metachromatic leukodystrophy, and has symptoms including seizures, gait ataxia and muscle spasticity. An important gene associated with Metachromatic Leukodystrophy Due to Saposin B Deficiency is PSAP (Prosaposin). Affiliated tissues include bone marrow, bone and brain, and related phenotypes are hyperreflexia and dysarthria

More information from OMIM: 249900

Related Diseases for Metachromatic Leukodystrophy Due to Saposin B Deficiency

Diseases related to Metachromatic Leukodystrophy Due to Saposin B Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 20)
# Related Disease Score Top Affiliating Genes
1 gm2-gangliosidosis, ab variant 11.5
2 metachromatic leukodystrophy 11.5
3 leukodystrophy 10.4
4 combined saposin deficiency 10.0
5 lysosomal disease 10.0
6 sandhoff disease 9.9
7 tay-sachs disease 9.9
8 krabbe disease 9.7
9 nephrotic syndrome 9.7
10 epilepsy 9.7
11 thrombophilia 9.7
12 gm2 gangliosidosis 9.7
13 arthropathy 9.7
14 brain edema 9.7
15 peripheral nervous system disease 9.7
16 conjunctivitis 9.7
17 arthritis 9.7
18 neuropathy 9.7
19 gangliosidosis 9.7
20 ligneous conjunctivitis 9.7

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



Diseases related to Metachromatic Leukodystrophy Due to Saposin B Deficiency

Symptoms & Phenotypes for Metachromatic Leukodystrophy Due to Saposin B Deficiency

Human phenotypes related to Metachromatic Leukodystrophy Due to Saposin B Deficiency:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 hyperreflexia 31 HP:0001347
2 dysarthria 31 HP:0001260
3 dysphagia 31 HP:0002015
4 muscle weakness 31 HP:0001324
5 developmental regression 31 HP:0002376
6 global developmental delay 31 HP:0001263
7 decreased nerve conduction velocity 31 HP:0000762
8 mental deterioration 31 HP:0001268
9 hyporeflexia 31 HP:0001265
10 gait ataxia 31 HP:0002066
11 babinski sign 31 HP:0003487
12 spastic tetraparesis 31 HP:0001285
13 polyneuropathy 31 HP:0001271
14 generalized hypotonia 31 HP:0001290
15 abnormality of the periventricular white matter 31 HP:0002518
16 loss of speech 31 HP:0002371
17 urinary incontinence 31 HP:0000020
18 peripheral demyelination 31 HP:0011096
19 cns demyelination 31 HP:0007305
20 seizure 31 HP:0001250
21 hypotonia 31 HP:0001252

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
spasticity
hyperreflexia
dysarthria
hyporeflexia
more
Neurologic Peripheral Nervous System:
peripheral neuropathy
hyporeflexia
decreased nerve conduction velocities

Muscle Soft Tissue:
weakness
hypotonia

Abdomen Gastrointestinal:
dysphagia

Genitourinary Bladder:
urinary incontinence

Laboratory Abnormalities:
normal or mildly decreased arylsulfatase a activity
saposin b deficiency
submucosal macrophages filled with sphingolipids
increased urinary sulfatides

Clinical features from OMIM®:

249900 (Updated 05-Apr-2021)

UMLS symptoms related to Metachromatic Leukodystrophy Due to Saposin B Deficiency:


seizures; gait ataxia; muscle spasticity; weakness

Drugs & Therapeutics for Metachromatic Leukodystrophy Due to Saposin B Deficiency

Search Clinical Trials , NIH Clinical Center for Metachromatic Leukodystrophy Due to Saposin B Deficiency

Genetic Tests for Metachromatic Leukodystrophy Due to Saposin B Deficiency

Anatomical Context for Metachromatic Leukodystrophy Due to Saposin B Deficiency

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

40
Bone Marrow, Bone, Brain, Liver

Publications for Metachromatic Leukodystrophy Due to Saposin B Deficiency

Articles related to Metachromatic Leukodystrophy Due to Saposin B Deficiency:

(show all 34)
# Title Authors PMID Year
1
Prosaposin deficiency and saposin B deficiency (activator-deficient metachromatic leukodystrophy): report on two patients detected by analysis of urinary sphingolipids and carrying novel PSAP gene mutations. 57 6 61
19267410 2009
2
A non-glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP-B) in a novel case of metachromatic leukodystrophy (MLD). 6 57
10682309 2000
3
Analysis of a splice-site mutation in the sap-precursor gene of a patient with metachromatic leukodystrophy. 57 6
8554069 1996
4
Metachromatic leukodystrophy without arylsulfatase A deficiency: a new case of saposin-B deficiency. 61 6
17616409 2008
5
Bone marrow transplantation in metachromatic leukodystrophy caused by saposin-B deficiency: a case report with a 3-year follow-up period. 61 57
9672525 1998
6
Characterization of a mutation in a family with saposin B deficiency: a glycosylation site defect. 6 61
2320574 1990
7
Late Infantile Metachromatic Leukodystrophy Due to Novel Pathogenic Variants in the PSAP Gene. 6
30632081 2019
8
Mutation Update of ARSA and PSAP Genes Causing Metachromatic Leukodystrophy. 6
26462614 2016
9
Saposin C mutations in Gaucher disease patients resulting in lysosomal lipid accumulation, saposin C deficiency, but normal prosaposin processing and sorting. 6
20484222 2010
10
Molecular analysis of ARSA and PSAP genes in twenty-one Italian patients with metachromatic leukodystrophy: identification and functional characterization of 11 novel ARSA alleles. 6
18693274 2008
11
Saposin B mobilizes lipids from cholesterol-poor and bis(monoacylglycero)phosphate-rich membranes at acidic pH. Unglycosylated patient variant saposin B lacks lipid-extraction capacity. 6
17561962 2007
12
A novel mutation in the coding region of the prosaposin gene leads to a complete deficiency of prosaposin and saposins, and is associated with a complex sphingolipidosis dominated by lactosylceramide accumulation. 6
11309366 2001
13
An Asn > Lys substitution in saposin B involving a conserved amino acidic residue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity. 6
10196694 1999
14
Correction of sulfatide metabolism after transfer of prosaposin cDNA to cultured cells from a patient with SAP-1 deficiency. 57
1350885 1992
15
Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene. 6
1371116 1992
16
The mechanism for a 33-nucleotide insertion in mRNA causing sphingolipid activator protein (SAP-1)-deficient metachromatic leukodystrophy. 6
2066109 1991
17
Sulfatide activator protein. Alternative splicing that generates three mRNAs and a newly found mutation responsible for a clinical disease. 6
2019586 1991
18
Insertion in the mRNA of a metachromatic leukodystrophy patient with sphingolipid activator protein-1 deficiency. 6
1689485 1990
19
Detection of a point mutation in sphingolipid activator protein-1 mRNA in patients with a variant form of metachromatic leukodystrophy. 6
2302219 1990
20
Clinical, pathological, and biochemical studies on an infantile case of sulfatide/GM1 activator protein deficiency. 57
2764035 1989
21
Genetic complementation in somatic cell hybrids of cerebroside sulfatase activator deficiency and metachromatic leukodystrophy fibroblasts. 57
6144627 1984
22
Concentrations of an activator protein for sphingolipid hydrolysis in liver and brain samples from patients with lysosomal storage diseases. 57
6415115 1983
23
Immunological evidence for deficiency in an activator protein for sulfatide sulfatase in a variant form of metachromatic leukodystrophy. 57
6134282 1983
24
A variant form of metachromatic leukodystrophy without arylsulfatase deficiency. 57
6126151 1982
25
Cerebroside sulfatase activator deficiency induced metachromatic leukodystrophy. 57
6119902 1981
26
Metachromatic leukodystrophy without arylsulfatase A deficiency. 57
41211 1979
27
The activator of cerebroside sulphatase. Binding studies with enzyme and substrate demonstrating the detergent function of the activator protein. 57
15613 1977
28
Comprehensive clinical, biochemical, radiological and genetic analysis of 28 Turkish cases with suspected metachromatic leukodystrophy and their relatives. 61
33335837 2020
29
Multiplex testing for the screening of lysosomal storage disease in urine: Sulfatides and glycosaminoglycan profiles in 40 cases of sulfatiduria. 61
31753749 2020
30
Saposin B-Deficient Metachromatic Leukodystrophy Mimicking Acute Flaccid Paralysis. 61
31319425 2019
31
Saposin B deficiency as a cause of adult-onset metachromatic leukodystrophy. 61
31289144 2019
32
Altered autophagy in the mice with a deficiency of saposin A and saposin B. 61
23697974 2013
33
Tissue-specific effects of saposin A and saposin B on glycosphingolipid degradation in mutant mice. 61
23446636 2013
34
[Saposin B deficiency]. 61
9645097 1998

Variations for Metachromatic Leukodystrophy Due to Saposin B Deficiency

ClinVar genetic disease variations for Metachromatic Leukodystrophy Due to Saposin B Deficiency:

6 (show top 50) (show all 128)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PSAP NM_002778.4(PSAP):c.1A>G (p.Met1Val) SNV Pathogenic 860182 GRCh37: 10:73610978-73610978
GRCh38: 10:71851221-71851221
2 PSAP NM_002778.4(PSAP):c.577-1G>T SNV Pathogenic 13366 rs1589451049 GRCh37: 10:73587915-73587915
GRCh38: 10:71828158-71828158
3 PSAP NM_002778.4(PSAP):c.577-2A>G SNV Pathogenic 13374 rs1589451050 GRCh37: 10:73587916-73587916
GRCh38: 10:71828159-71828159
4 PSAP PSAP, IVS4AS, C-A SNV Pathogenic 13362 GRCh37:
GRCh38:
5 PSAP NM_002778.4(PSAP):c.643A>C (p.Asn215His) SNV Pathogenic 13367 rs121918107 GRCh37: 10:73587848-73587848
GRCh38: 10:71828091-71828091
6 PSAP NM_002778.4(PSAP):c.1268del (p.Leu423fs) Deletion Pathogenic 562227 rs1564815053 GRCh37: 10:73579304-73579304
GRCh38: 10:71819547-71819547
7 PSAP NM_002778.4(PSAP):c.1348C>T (p.Gln450Ter) SNV Pathogenic 942712 GRCh37: 10:73579224-73579224
GRCh38: 10:71819467-71819467
8 PSAP NM_002778.4(PSAP):c.1369G>T (p.Glu457Ter) SNV Pathogenic 438801 rs1554879741 GRCh37: 10:73578850-73578850
GRCh38: 10:71819093-71819093
9 PSAP NM_002778.4(PSAP):c.826_827GA[1] (p.Glu276fs) Microsatellite Pathogenic 13375 rs1589448124 GRCh37: 10:73581713-73581714
GRCh38: 10:71821956-71821957
10 PSAP NM_002778.4(PSAP):c.722G>C (p.Cys241Ser) SNV Pathogenic 13363 rs121918104 GRCh37: 10:73585649-73585649
GRCh38: 10:71825892-71825892
11 PSAP NM_002778.4(PSAP):c.645C>A (p.Asn215Lys) SNV Likely pathogenic 857581 GRCh37: 10:73587846-73587846
GRCh38: 10:71828089-71828089
12 PSAP NM_002778.4(PSAP):c.721-1G>A SNV Likely pathogenic 968905 GRCh37: 10:73585651-73585651
GRCh38: 10:71825894-71825894
13 PSAP NC_000010.11:g.(?_71828004)_(71834515_?)dup Duplication Likely pathogenic 832143 GRCh37: 10:73587761-73594272
GRCh38:
14 PSAP NM_002778.4(PSAP):c.679_681del (p.Lys227del) Deletion Likely pathogenic 562226 rs1431844269 GRCh37: 10:73587810-73587812
GRCh38: 10:71828053-71828055
15 PSAP NM_002778.4(PSAP):c.650C>T (p.Thr217Ile) SNV Likely pathogenic 13361 rs121918103 GRCh37: 10:73587841-73587841
GRCh38: 10:71828084-71828084
16 PSAP NM_002778.4(PSAP):c.714C>G (p.Ala238=) SNV Conflicting interpretations of pathogenicity 300522 rs141199649 GRCh37: 10:73587777-73587777
GRCh38: 10:71828020-71828020
17 PSAP NM_002778.4(PSAP):c.1476T>C (p.Thr492=) SNV Conflicting interpretations of pathogenicity 300507 rs139178900 GRCh37: 10:73578437-73578437
GRCh38: 10:71818680-71818680
18 PSAP NM_002778.4(PSAP):c.174+9C>T SNV Conflicting interpretations of pathogenicity 300532 rs141133813 GRCh37: 10:73594120-73594120
GRCh38: 10:71834363-71834363
19 PSAP NM_002778.4(PSAP):c.577-10T>C SNV Conflicting interpretations of pathogenicity 300523 rs185892516 GRCh37: 10:73587924-73587924
GRCh38: 10:71828167-71828167
20 PSAP NM_002778.4(PSAP):c.1278C>T (p.Asn426=) SNV Conflicting interpretations of pathogenicity 300511 rs777227555 GRCh37: 10:73579294-73579294
GRCh38: 10:71819537-71819537
21 PSAP NM_002778.4(PSAP):c.1146C>T (p.Cys382=) SNV Conflicting interpretations of pathogenicity 765408 rs573095617 GRCh37: 10:73579517-73579517
GRCh38: 10:71819760-71819760
22 PSAP NM_002778.4(PSAP):c.189C>T (p.Cys63=) SNV Conflicting interpretations of pathogenicity 300531 rs111369573 GRCh37: 10:73591663-73591663
GRCh38: 10:71831906-71831906
23 PSAP NM_002778.4(PSAP):c.1056C>T (p.Ser352=) SNV Conflicting interpretations of pathogenicity 300516 rs138328594 GRCh37: 10:73579607-73579607
GRCh38: 10:71819850-71819850
24 PSAP NM_002778.4(PSAP):c.161A>G (p.Asn54Ser) SNV Uncertain significance 1001440 GRCh37: 10:73594142-73594142
GRCh38: 10:71834385-71834385
25 PSAP NM_002778.4(PSAP):c.794G>A (p.Cys265Tyr) SNV Uncertain significance 1004559 GRCh37: 10:73581748-73581748
GRCh38: 10:71821991-71821991
26 PSAP NM_002778.4(PSAP):c.1172C>T (p.Thr391Met) SNV Uncertain significance 300514 rs202125074 GRCh37: 10:73579491-73579491
GRCh38: 10:71819734-71819734
27 PSAP NM_002778.4(PSAP):c.*1008C>T SNV Uncertain significance 877646 GRCh37: 10:73576190-73576190
GRCh38: 10:71816433-71816433
28 PSAP NM_002778.4(PSAP):c.*526G>A SNV Uncertain significance 877692 GRCh37: 10:73576672-73576672
GRCh38: 10:71816915-71816915
29 PSAP NM_002778.4(PSAP):c.*90C>T SNV Uncertain significance 877730 GRCh37: 10:73577108-73577108
GRCh38: 10:71817351-71817351
30 PSAP NM_002778.4(PSAP):c.565C>T (p.Pro189Ser) SNV Uncertain significance 878037 GRCh37: 10:73588645-73588645
GRCh38: 10:71828888-71828888
31 PSAP NM_002778.4(PSAP):c.249+6C>T SNV Uncertain significance 878088 GRCh37: 10:73591597-73591597
GRCh38: 10:71831840-71831840
32 PSAP NM_002778.4(PSAP):c.*376A>G SNV Uncertain significance 877693 GRCh37: 10:73576822-73576822
GRCh38: 10:71817065-71817065
33 PSAP NM_002778.4(PSAP):c.*346C>T SNV Uncertain significance 878721 GRCh37: 10:73576852-73576852
GRCh38: 10:71817095-71817095
34 PSAP NM_002778.4(PSAP):c.1329G>T (p.Leu443=) SNV Uncertain significance 878804 GRCh37: 10:73579243-73579243
GRCh38: 10:71819486-71819486
35 PSAP NM_002778.4(PSAP):c.*787C>T SNV Uncertain significance 878665 GRCh37: 10:73576411-73576411
GRCh38: 10:71816654-71816654
36 PSAP NM_002778.4(PSAP):c.*737G>A SNV Uncertain significance 879264 GRCh37: 10:73576461-73576461
GRCh38: 10:71816704-71816704
37 CDH23 , PSAP NM_002778.4(PSAP):c.*238G>C SNV Uncertain significance 879308 GRCh37: 10:73576960-73576960
GRCh38: 10:71817203-71817203
38 PSAP NM_002778.4(PSAP):c.1197C>T (p.His399=) SNV Uncertain significance 879388 GRCh37: 10:73579375-73579375
GRCh38: 10:71819618-71819618
39 PSAP NM_002778.4(PSAP):c.508C>G (p.Pro170Ala) SNV Uncertain significance 879499 GRCh37: 10:73588702-73588702
GRCh38: 10:71828945-71828945
40 PSAP NM_002778.4(PSAP):c.423C>T (p.Leu141=) SNV Uncertain significance 879500 GRCh37: 10:73588787-73588787
GRCh38: 10:71829030-71829030
41 PSAP NM_002778.4(PSAP):c.419C>T (p.Ser140Phe) SNV Uncertain significance 879866 GRCh37: 10:73588791-73588791
GRCh38: 10:71829034-71829034
42 PSAP NM_002778.4(PSAP):c.*596A>G SNV Uncertain significance 880453 GRCh37: 10:73576602-73576602
GRCh38: 10:71816845-71816845
43 PSAP NM_002778.4(PSAP):c.613_615dup (p.Val205dup) Duplication Uncertain significance 813908 rs1589451004 GRCh37: 10:73587875-73587876
GRCh38: 10:71828118-71828119
44 PSAP NM_002778.4(PSAP):c.250-12G>A SNV Uncertain significance 300528 rs886047152 GRCh37: 10:73591020-73591020
GRCh38: 10:71831263-71831263
45 PSAP NM_002778.4(PSAP):c.415G>A (p.Glu139Lys) SNV Uncertain significance 650590 rs753606836 GRCh37: 10:73588795-73588795
GRCh38: 10:71829038-71829038
46 PSAP NM_002778.4(PSAP):c.638G>A (p.Arg213Gln) SNV Uncertain significance 662707 rs773913014 GRCh37: 10:73587853-73587853
GRCh38: 10:71828096-71828096
47 PSAP NM_002778.4(PSAP):c.*73C>T SNV Uncertain significance 300505 rs541692197 GRCh37: 10:73577125-73577125
GRCh38: 10:71817368-71817368
48 PSAP NM_002778.4(PSAP):c.*574G>C SNV Uncertain significance 300501 rs549402343 GRCh37: 10:73576624-73576624
GRCh38: 10:71816867-71816867
49 PSAP NM_002778.4(PSAP):c.911A>G (p.Lys304Arg) SNV Uncertain significance 300520 rs757553906 GRCh37: 10:73580091-73580091
GRCh38: 10:71820334-71820334
50 PSAP NM_002778.4(PSAP):c.1088C>T (p.Thr363Met) SNV Uncertain significance 300515 rs140066253 GRCh37: 10:73579575-73579575
GRCh38: 10:71819818-71819818

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

72
# Symbol AA change Variation ID SNP ID
1 PSAP p.Thr217Ile VAR_006943 rs121918103
2 PSAP p.Cys241Ser VAR_006944 rs121918104
3 PSAP p.Asn215His VAR_031823 rs121918107
4 PSAP p.Asn215Lys VAR_031899 rs770171865

Expression for Metachromatic Leukodystrophy Due to Saposin B Deficiency

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

Pathways for Metachromatic Leukodystrophy Due to Saposin B Deficiency

GO Terms for Metachromatic Leukodystrophy Due to Saposin B Deficiency

Sources for Metachromatic Leukodystrophy Due to Saposin B Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
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19 FMA
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28 GO
29 GTR
30 HMDB
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32 ICD10
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61 PubMed
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71 UMLS via Orphanet
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