CSAPD
MCID: CMB020
MIFTS: 37

Combined Saposin Deficiency (CSAPD)

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

Aliases & Classifications for Combined Saposin Deficiency

MalaCards integrated aliases for Combined Saposin Deficiency:

Name: Combined Saposin Deficiency 57 12 53 74 29 6 72
Combined Sap Deficiency 57 12 53 37 13
Encephalopathy Due to Prosaposin Deficiency 12 53 59
Prosaposin Deficiency 57 53 74
Psapd 57 12 53
Combined Prosaposin Deficiency 53 59
Prosaposin Deficiency; Psapd 57
Saposin Deficiency, Combined 40
Csapd 74

Characteristics:

Orphanet epidemiological data:

59
encephalopathy due to prosaposin deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Miscellaneous:
death in infancy
onset at birth

Inheritance:
autosomal recessive


HPO:

32
combined saposin deficiency:
Clinical modifier death in infancy
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0111330
OMIM 57 611721
KEGG 37 H01239
ICD10 via Orphanet 34 E75.2
Orphanet 59 ORPHA139406
MedGen 42 C2673635
UMLS 72 C2673635

Summaries for Combined Saposin Deficiency

KEGG : 37
Combined SAP deficiency is a fatal infantile lysosomal storage disorder with hepatosplenomegaly and severe neurological disease. It is caused by mutations in the PSAP gene leading to absence or non-functionality of the prosaposin protein. Mammalian prosaposin encodes in tandem four small acidic activator proteins (saposins) with specificities for glycosphingolipids hydrolases.

MalaCards based summary : Combined Saposin Deficiency, also known as combined sap deficiency, is related to metachromatic leukodystrophy and leukodystrophy, and has symptoms including myoclonus and muscular fasciculation. An important gene associated with Combined Saposin Deficiency is PSAP (Prosaposin), and among its related pathways/superpathways is Lysosome. Affiliated tissues include brain, eye and breast, and related phenotypes are abnormality of eye movement and muscular hypotonia

Disease Ontology : 12 A sphingolipidosis characterized by absence of expression of both isoforms of PSAP (SAP1 and SAP2) resulting in hepatosplenomegaly and severe neurological disease that has material basis in homozygous or coumpound heterozygous mutation in PSAP on 10q22.1.

UniProtKB/Swiss-Prot : 74 Combined saposin deficiency: Due to absence of all saposins, leading to a fatal storage disorder with hepatosplenomegaly and severe neurological involvement.

More information from OMIM: 611721

Related Diseases for Combined Saposin Deficiency

Diseases related to Combined Saposin Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 20)
# Related Disease Score Top Affiliating Genes
1 metachromatic leukodystrophy 29.0 PSAP CDH23
2 leukodystrophy 10.1
3 lysosomal storage disease 10.1
4 gm2 gangliosidosis 10.1
5 farber lipogranulomatosis 10.0
6 gaucher disease, type i 10.0
7 gaucher disease, type ii 10.0
8 krabbe disease 10.0
9 metachromatic leukodystrophy due to saposin b deficiency 10.0
10 neuraminidase deficiency 10.0
11 niemann-pick disease, type c1 10.0
12 gaucher disease, atypical, due to saposin c deficiency 10.0
13 protein-losing enteropathy 10.0
14 niemann-pick disease 10.0
15 gaucher's disease 10.0
16 glycoproteinosis 10.0
17 lipid storage disease 10.0
18 gangliosidosis 10.0
19 myoclonus 10.0
20 retinitis pigmentosa 9.2 PSAP CDH23

Graphical network of the top 20 diseases related to Combined Saposin Deficiency:



Diseases related to Combined Saposin Deficiency

Symptoms & Phenotypes for Combined Saposin Deficiency

Human phenotypes related to Combined Saposin Deficiency:

59 32 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of eye movement 59 32 hallmark (90%) Very frequent (99-80%) HP:0000496
2 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
3 respiratory insufficiency 59 32 hallmark (90%) Very frequent (99-80%) HP:0002093
4 splenomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001744
5 recurrent respiratory infections 59 32 hallmark (90%) Very frequent (99-80%) HP:0002205
6 hepatomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0002240
7 myoclonus 59 32 hallmark (90%) Very frequent (99-80%) HP:0001336
8 dystonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001332
9 generalized tonic-clonic seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0002069
10 optic atrophy 32 occasional (7.5%) HP:0000648
11 generalized hypotonia 32 HP:0001290
12 feeding difficulties 32 HP:0011968
13 death in infancy 59 Very frequent (99-80%)
14 abnormality of glycosphingolipid metabolism 32 HP:0004343
15 babinski sign 32 HP:0003487
16 fasciculations 32 HP:0002380
17 hypoplasia of the corpus callosum 32 HP:0002079
18 abnormality of the periventricular white matter 32 HP:0002518
19 neuronal loss in central nervous system 32 HP:0002529
20 hyperkinesis 32 HP:0002487
21 generalized clonic seizures 32 HP:0011169
22 cns demyelination 32 HP:0007305

Symptoms via clinical synopsis from OMIM:

57
Abdomen Spleen:
splenomegaly

Neurologic Central Nervous System:
myoclonus
fasciculations
hypotonia
neuronal loss
extensor plantar responses
more
Head And Neck Eyes:
optic atrophy (reported in 1 patient)

Laboratory Abnormalities:
multiple tissue biopsies show lysosomal storage disease
deficiency of saposins a, b, c, and d
decreased activity of glycosylceramidase, galactosylceramidase, ceramidase, and other lysosomal enzymes
increased urinary glycosphingolipids, particularly globotriaosylceramide

Abdomen Liver:
hepatomegaly

Abdomen Gastrointestinal:
poor feeding

Respiratory:
neonatal respiratory failure

Clinical features from OMIM:

611721

UMLS symptoms related to Combined Saposin Deficiency:


myoclonus, muscular fasciculation

MGI Mouse Phenotypes related to Combined Saposin Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hearing/vestibular/ear MP:0005377 8.62 CDH23 PSAP

Drugs & Therapeutics for Combined Saposin Deficiency

Search Clinical Trials , NIH Clinical Center for Combined Saposin Deficiency

Genetic Tests for Combined Saposin Deficiency

Genetic tests related to Combined Saposin Deficiency:

# Genetic test Affiliating Genes
1 Combined Saposin Deficiency 29 PSAP

Anatomical Context for Combined Saposin Deficiency

MalaCards organs/tissues related to Combined Saposin Deficiency:

41
Brain, Eye, Breast, Skin

Publications for Combined Saposin Deficiency

Articles related to Combined Saposin Deficiency:

(show all 31)
# 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. 8 71
19267410 2009
2
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. 8 71
11309366 2001
3
Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene. 8 71
1371116 1992
4
Sphingolipid activator protein deficiency in a 16-week-old atypical Gaucher disease patient and his fetal sibling: biochemical signs of combined sphingolipidoses. 8 71
2514102 1989
5
Non-neuronopathic Gaucher disease due to saposin C deficiency. 71
17919309 2007
6
Prosaposin deficiency: further characterization of the sphingolipid activator protein-deficient sibs. Multiple glycolipid elevations (including lactosylceramidosis), partial enzyme deficiencies and ultrastructure of the skin in this generalized sphingolipid storage disease. 71
8370580 1993
7
Thermal regulation of tightly packed solid-state photodetectors in a 1 mm(3) resolution clinical PET system. 38
25563270 2015
8
Thermal regulation for APDs in a 1 mm(3) resolution clinical PET camera: design, simulation and experimental verification. 38
24971652 2014
9
Betabox: a beta particle imaging system based on a position sensitive avalanche photodiode. 38
23656911 2013
10
Signal and noise properties of position-sensitive avalanche photodiodes. 38
21896961 2011
11
Temperature dependent operation of PSAPD-based compact gamma camera for SPECT imaging. 38
24465051 2011
12
Convex optimization of coincidence time resolution for a high-resolution PET system. 38
20876008 2011
13
Analog signal multiplexing for PSAPD-based PET detectors: simulation and experimental validation. 38
21081831 2010
14
Phantom experiments on a PSAPD-based compact gamma camera with submillimeter spatial resolution for small animal SPECT. 38
21278833 2010
15
Effects of multiple-interaction photon events in a high-resolution PET system that uses 3-D positioning detectors. 38
21089785 2010
16
A study of the timing properties of position-sensitive avalanche photodiodes. 38
19671971 2009
17
PET Performance Evaluation of an MR-Compatible PET Insert. 38
21072320 2009
18
Spatial distortion correction and crystal identification for MRI-compatible position-sensitive avalanche photodiode-based PET scanners. 38
20161023 2009
19
Crystal identification in positron emission tomography using nonrigid registration to a Fourier-based template. 38
18723924 2008
20
A prototype PET scanner with DOI-encoding detectors. 38
18552140 2008
21
Effects of system geometry and other physical factors on photon sensitivity of high-resolution positron emission tomography. 38
17664575 2007
22
Monte Carlo simulations of compact gamma cameras based on avalanche photodiodes. 38
17505089 2007
23
A New Positioning Algorithm for Position-Sensitive Avalanche Photodiodes. 38
24307743 2007
24
Study of the performance of a novel 1 mm resolution dual-panel PET camera design dedicated to breast cancer imaging using Monte Carlo simulation. 38
17388187 2007
25
Posterior sagittal approach with perirectal dissection for reconstructive surgery of severe urogenital anomalies. 38
17072623 2007
26
Simultaneous acquisition of multislice PET and MR images: initial results with a MR-compatible PET scanner. 38
17138739 2006
27
A multipinhole small animal SPECT system with submillimeter spatial resolution. 38
16752560 2006
28
Depth of interaction resolution measurements for a high resolution PET detector using position sensitive avalanche photodiodes. 38
16625031 2006
29
Evaluation of a dual-panel PET camera design to breast cancer imaging. 38
17646005 2006
30
Impact of high energy resolution detectors on the performance of a PET system dedicated to breast cancer imaging. 38
17645990 2006
31
Does the posterior sagittal approach with perirectal dissection impair fecal continence in a normal rectum? 38
8906658 1996

Variations for Combined Saposin Deficiency

ClinVar genetic disease variations for Combined Saposin Deficiency:

6 (show top 50) (show all 94)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 PSAP NM_001042465.3(PSAP): c.1378G> T (p.Glu460Ter) single nucleotide variant Pathogenic rs1554879741 10:73578850-73578850 10:71819093-71819093
2 PSAP NM_001042465.3(PSAP): c.722G> C (p.Cys241Ser) single nucleotide variant Pathogenic rs121918104 10:73585649-73585649 10:71825892-71825892
3 PSAP NM_001042465.3(PSAP): c.1A> T (p.Met1Leu) single nucleotide variant Pathogenic rs121918106 10:73610978-73610978 10:71851221-71851221
4 PSAP PSAP, 1-BP DEL, 803G deletion Pathogenic
5 PSAP PSAP, IVS9AS, A-G, -2 single nucleotide variant Pathogenic
6 CDH23 ; PSAP NM_022124.6(CDH23): c.9983G> A (p.Arg3328His) single nucleotide variant Conflicting interpretations of pathogenicity rs148475933 10:73574953-73574953 10:71815196-71815196
7 CDH23 ; PSAP NM_022124.6(CDH23): c.9629T> C (p.Ile3210Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs144688588 10:73572643-73572643 10:71812886-71812886
8 CDH23 ; PSAP NM_022124.6(CDH23): c.10026C> T (p.Asp3342=) single nucleotide variant Conflicting interpretations of pathogenicity rs377118941 10:73574996-73574996 10:71815239-71815239
9 CDH23 ; PSAP NM_022124.5(CDH23): c.9510+16_9510+22delTCAGGCA deletion Conflicting interpretations of pathogenicity rs149704197 10:73572385-73572391 10:71812628-71812634
10 CDH23 ; PSAP NM_022124.6(CDH23): c.9739-12G> A single nucleotide variant Conflicting interpretations of pathogenicity rs200638595 10:73574697-73574697 10:71814940-71814940
11 CDH23 ; PSAP NM_022124.6(CDH23): c.*68G> C single nucleotide variant Conflicting interpretations of pathogenicity rs527311705 10:73575103-73575103 10:71815346-71815346
12 CDH23 ; PSAP NM_022124.6(CDH23): c.9291G> T (p.Lys3097Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs368441850 10:73571482-73571482 10:71811725-71811725
13 CDH23 ; PSAP NM_022124.6(CDH23): c.9860G> A (p.Gly3287Asp) single nucleotide variant Conflicting interpretations of pathogenicity rs562590210 10:73574830-73574830 10:71815073-71815073
14 CDH23 ; PSAP NM_022124.6(CDH23): c.*515C> A single nucleotide variant Conflicting interpretations of pathogenicity rs16929375 10:73575550-73575550 10:71815793-71815793
15 CDH23 ; PSAP NM_022124.6(CDH23): c.9942G> A (p.Thr3314=) single nucleotide variant Conflicting interpretations of pathogenicity rs376804660 10:73574912-73574912 10:71815155-71815155
16 CDH23 ; PSAP NM_022124.6(CDH23): c.*361C> A single nucleotide variant Conflicting interpretations of pathogenicity rs115033851 10:73575396-73575396 10:71815639-71815639
17 CDH23 ; PSAP NM_022124.6(CDH23): c.*430A> T single nucleotide variant Conflicting interpretations of pathogenicity rs562268606 10:73575465-73575465 10:71815708-71815708
18 CDH23 ; PSAP NM_022124.6(CDH23): c.*434G> A single nucleotide variant Conflicting interpretations of pathogenicity rs529522213 10:73575469-73575469 10:71815712-71815712
19 CDH23 ; PSAP NM_022124.6(CDH23): c.*588del deletion Conflicting interpretations of pathogenicity rs148667421 10:73575623-73575623 10:71815866-71815866
20 CDH23 ; PSAP NM_022124.6(CDH23): c.9799C> T (p.Arg3267Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs201727938 10:73574769-73574769 10:71815012-71815012
21 CDH23 ; PSAP NM_022124.6(CDH23): c.*104G> C single nucleotide variant Conflicting interpretations of pathogenicity rs377312107 10:73575139-73575139 10:71815382-71815382
22 CDH23 ; PSAP NM_022124.6(CDH23): c.*141G> A single nucleotide variant Conflicting interpretations of pathogenicity rs535544696 10:73575176-73575176 10:71815419-71815419
23 PSAP NM_001042465.3(PSAP): c.932C> T (p.Pro311Leu) single nucleotide variant Uncertain significance rs886047150 10:73580079-73580079 10:71820322-71820322
24 PSAP NM_001042465.3(PSAP): c.807G> A (p.Ala269=) single nucleotide variant Uncertain significance rs199672678 10:73581744-73581744 10:71821987-71821987
25 PSAP NM_001042465.3(PSAP): c.1287C> T (p.Asn429=) single nucleotide variant Uncertain significance rs777227555 10:73579294-73579294 10:71819537-71819537
26 PSAP NM_001042465.3(PSAP): c.1097C> T (p.Thr366Met) single nucleotide variant Uncertain significance rs140066253 10:73579575-73579575 10:71819818-71819818
27 PSAP NM_001042465.3(PSAP): c.*859C> T single nucleotide variant Uncertain significance rs886047149 10:73576339-73576339 10:71816582-71816582
28 PSAP NM_001042465.3(PSAP): c.1465C> T (p.His489Tyr) single nucleotide variant Uncertain significance rs749660716 10:73578457-73578457 10:71818700-71818700
29 PSAP NM_001042465.3(PSAP): c.1009A> T (p.Thr337Ser) single nucleotide variant Uncertain significance rs749663645 10:73580002-73580002 10:71820245-71820245
30 PSAP NM_002778.3(PSAP): c.-99T> G single nucleotide variant Uncertain significance rs886047156 10:73611077-73611077 10:71851320-71851320
31 PSAP NM_001042465.3(PSAP): c.94T> G (p.Trp32Gly) single nucleotide variant Uncertain significance rs200008050 10:73594209-73594209 10:71834452-71834452
32 PSAP NM_001042465.3(PSAP): c.*113C> T single nucleotide variant Uncertain significance rs544214520 10:73577085-73577085 10:71817328-71817328
33 PSAP NM_001042465.3(PSAP): c.1441-4A> G single nucleotide variant Uncertain significance rs775086571 10:73578485-73578485 10:71818728-71818728
34 PSAP NM_001042465.3(PSAP): c.1181C> T (p.Thr394Met) single nucleotide variant Uncertain significance rs202125074 10:73579491-73579491 10:71819734-71819734
35 PSAP NM_001042465.3(PSAP): c.920A> G (p.Lys307Arg) single nucleotide variant Uncertain significance rs757553906 10:73580091-73580091 10:71820334-71820334
36 PSAP NM_001042465.3(PSAP): c.380G> A (p.Arg127His) single nucleotide variant Uncertain significance rs886047151 10:73588830-73588830 10:71829073-71829073
37 PSAP NM_001042465.3(PSAP): c.*935A> G single nucleotide variant Uncertain significance rs886047148 10:73576263-73576263 10:71816506-71816506
38 PSAP NM_001042465.3(PSAP): c.*9A> G single nucleotide variant Uncertain significance rs376628499 10:73577189-73577189 10:71817432-71817432
39 PSAP NM_002778.3(PSAP): c.-56A> G single nucleotide variant Uncertain significance rs534586960 10:73611034-73611034 10:71851277-71851277
40 PSAP NM_002778.3(PSAP): c.-62A> G single nucleotide variant Uncertain significance rs886047155 10:73611040-73611040 10:71851283-71851283
41 PSAP NM_001042465.3(PSAP): c.1267G> A (p.Asp423Asn) single nucleotide variant Uncertain significance rs760621775 10:73579314-73579314 10:71819557-71819557
42 PSAP NM_001042465.3(PSAP): c.557G> A (p.Arg186His) single nucleotide variant Uncertain significance rs138880818 10:73588653-73588653 10:71828896-71828896
43 PSAP NM_001042465.3(PSAP): c.250-12G> A single nucleotide variant Uncertain significance rs886047152 10:73591020-73591020 10:71831263-71831263
44 PSAP NM_001042465.3(PSAP): c.112A> T (p.Thr38Ser) single nucleotide variant Uncertain significance rs535525554 10:73594191-73594191 10:71834434-71834434
45 PSAP NM_002778.3(PSAP): c.-50G> T single nucleotide variant Uncertain significance rs886047154 10:73611028-73611028 10:71851271-71851271
46 PSAP NM_001042465.3(PSAP): c.40+12G> A single nucleotide variant Uncertain significance rs886047153 10:73610927-73610927 10:71851170-71851170
47 PSAP NM_001042465.3(PSAP): c.78C> T (p.Thr26=) single nucleotide variant Likely benign rs74145688 10:73594225-73594225 10:71834468-71834468
48 PSAP NM_001042465.3(PSAP): c.167C> G (p.Pro56Arg) single nucleotide variant Likely benign rs571773332 10:73594136-73594136 10:71834379-71834379
49 PSAP NM_001042465.3(PSAP): c.714C> G (p.Ala238=) single nucleotide variant Likely benign rs141199649 10:73587777-73587777 10:71828020-71828020
50 PSAP NM_001042465.3(PSAP): c.1461G> A (p.Ser487=) single nucleotide variant Likely benign rs114389264 10:73578461-73578461 10:71818704-71818704

Expression for Combined Saposin Deficiency

Search GEO for disease gene expression data for Combined Saposin Deficiency.

Pathways for Combined Saposin Deficiency

Pathways related to Combined Saposin Deficiency according to KEGG:

37
# Name Kegg Source Accession
1 Lysosome hsa04142

GO Terms for Combined Saposin Deficiency

Sources for Combined Saposin Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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