CSAPD
MCID: CMB020
MIFTS: 31

Combined Saposin Deficiency (CSAPD)

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

Aliases & Classifications for Combined Saposin Deficiency

MalaCards integrated aliases for Combined Saposin Deficiency:

Name: Combined Saposin Deficiency 58 76 30 6 74
Combined Sap Deficiency 58 38 13
Prosaposin Deficiency 58 76
Encephalopathy Due to Prosaposin Deficiency 60
Combined Prosaposin Deficiency 60
Prosaposin Deficiency; Psapd 58
Saposin Deficiency, Combined 41
Prosaposin 13
Psapd 58
Csapd 76

Characteristics:

Orphanet epidemiological data:

60
encephalopathy due to prosaposin deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Miscellaneous:
death in infancy
onset at birth

Inheritance:
autosomal recessive


HPO:

33
combined saposin deficiency:
Mortality/Aging death in infancy
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Combined Saposin Deficiency

UniProtKB/Swiss-Prot : 76 Combined saposin deficiency: Due to absence of all saposins, leading to a fatal storage disorder with hepatosplenomegaly and severe neurological involvement.

MalaCards based summary : Combined Saposin Deficiency, also known as combined sap deficiency, is related to metachromatic leukodystrophy and encephalopathy due to prosaposin deficiency, 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 skin, and related phenotypes are optic atrophy and splenomegaly

Description from OMIM: 611721

Related Diseases for Combined Saposin Deficiency

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:

33 60 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 optic atrophy 33 occasional (7.5%) HP:0000648
2 splenomegaly 60 33 Very frequent (99-80%) HP:0001744
3 hepatomegaly 60 33 Very frequent (99-80%) HP:0002240
4 myoclonus 60 33 Very frequent (99-80%) HP:0001336
5 abnormality of eye movement 60 Very frequent (99-80%)
6 muscular hypotonia 60 Very frequent (99-80%)
7 respiratory insufficiency 60 Very frequent (99-80%)
8 recurrent respiratory infections 60 Very frequent (99-80%)
9 feeding difficulties 33 HP:0011968
10 death in infancy 60 Very frequent (99-80%)
11 abnormality of glycosphingolipid metabolism 33 HP:0004343
12 babinski sign 33 HP:0003487
13 dystonia 60 Very frequent (99-80%)
14 generalized tonic-clonic seizures 60 Very frequent (99-80%)
15 fasciculations 33 HP:0002380
16 generalized hypotonia 33 HP:0001290
17 hypoplasia of the corpus callosum 33 HP:0002079
18 abnormality of the periventricular white matter 33 HP:0002518
19 hyperkinesis 33 HP:0002487
20 neuronal loss in central nervous system 33 HP:0002529
21 cns demyelination 33 HP:0007305
22 generalized clonic seizures 33 HP:0011169

Symptoms via clinical synopsis from OMIM:

58
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:

47
# 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 30 PSAP

Anatomical Context for Combined Saposin Deficiency

MalaCards organs/tissues related to Combined Saposin Deficiency:

42
Brain, Eye, Skin

Publications for Combined Saposin Deficiency

Articles related to Combined Saposin Deficiency:

# Title Authors Year
1
Clinical, biochemical and molecular characterization of prosaposin deficiency. ( 26831127 )
2016
2
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. ( 19267410 )
2009
3
Neurolysosomal pathology in human prosaposin deficiency suggests essential neurotrophic function of prosaposin. ( 17024494 )
2007
4
Prosaposin deficiency -- a rarely diagnosed, rapidly progressing, neonatal neurovisceral lipid storage disease. Report of a further patient. ( 15944902 )
2005
5
Quantification of mRNAs encoding proteins of the glycosphingolipid catabolism in mouse models of GM2 gangliosidoses and sphingolipid activator protein precursor (prosaposin) deficiency. ( 11068181 )
2000
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. ( 8370580 )
1993

Variations for Combined Saposin Deficiency

ClinVar genetic disease variations for Combined Saposin Deficiency:

6 (show top 50) (show all 186)
# Gene Variation Type Significance SNP ID Assembly Location
1 CDH23; PSAP NM_022124.5(CDH23): c.9510+13C> T single nucleotide variant Benign/Likely benign rs183692794 GRCh38 Chromosome 10, 71812622: 71812622
2 CDH23; PSAP NM_022124.5(CDH23): c.9510+13C> T single nucleotide variant Benign/Likely benign rs183692794 GRCh37 Chromosome 10, 73572379: 73572379
3 CDH23; PSAP NM_022124.5(CDH23): c.9629T> C (p.Ile3210Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs144688588 GRCh38 Chromosome 10, 71812886: 71812886
4 CDH23; PSAP NM_022124.5(CDH23): c.9629T> C (p.Ile3210Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs144688588 GRCh37 Chromosome 10, 73572643: 73572643
5 CDH23; PSAP NM_022124.5(CDH23): c.10026C> T (p.Asp3342=) single nucleotide variant Conflicting interpretations of pathogenicity rs377118941 GRCh38 Chromosome 10, 71815239: 71815239
6 CDH23; PSAP NM_022124.5(CDH23): c.10026C> T (p.Asp3342=) single nucleotide variant Conflicting interpretations of pathogenicity rs377118941 GRCh37 Chromosome 10, 73574996: 73574996
7 PSAP NM_001042465.2(PSAP): c.722G> C (p.Cys241Ser) single nucleotide variant Pathogenic rs121918104 GRCh37 Chromosome 10, 73585649: 73585649
8 PSAP NM_001042465.2(PSAP): c.722G> C (p.Cys241Ser) single nucleotide variant Pathogenic rs121918104 GRCh38 Chromosome 10, 71825892: 71825892
9 PSAP NM_001042465.2(PSAP): c.1A> T (p.Met1Leu) single nucleotide variant Pathogenic rs121918106 GRCh37 Chromosome 10, 73610978: 73610978
10 PSAP NM_001042465.2(PSAP): c.1A> T (p.Met1Leu) single nucleotide variant Pathogenic rs121918106 GRCh38 Chromosome 10, 71851221: 71851221
11 PSAP PSAP, 1-BP DEL, 803G deletion Pathogenic
12 PSAP PSAP, IVS9AS, A-G, -2 single nucleotide variant Pathogenic
13 CDH23; PSAP NM_022124.5(CDH23): c.9319+11G> A single nucleotide variant Benign/Likely benign rs11000013 GRCh37 Chromosome 10, 73571521: 73571521
14 CDH23; PSAP NM_022124.5(CDH23): c.9319+11G> A single nucleotide variant Benign/Likely benign rs11000013 GRCh38 Chromosome 10, 71811764: 71811764
15 CDH23; PSAP NM_022124.5(CDH23): c.9373T> C (p.Phe3125Leu) single nucleotide variant Benign/Likely benign rs45583140 GRCh37 Chromosome 10, 73571765: 73571765
16 CDH23; PSAP NM_022124.5(CDH23): c.9373T> C (p.Phe3125Leu) single nucleotide variant Benign/Likely benign rs45583140 GRCh38 Chromosome 10, 71812008: 71812008
17 CDH23; PSAP NM_022124.5(CDH23): c.9501G> A (p.Thr3167=) single nucleotide variant Benign/Likely benign rs144906721 GRCh37 Chromosome 10, 73572357: 73572357
18 CDH23; PSAP NM_022124.5(CDH23): c.9501G> A (p.Thr3167=) single nucleotide variant Benign/Likely benign rs144906721 GRCh38 Chromosome 10, 71812600: 71812600
19 CDH23; PSAP NM_022124.5(CDH23): c.9758A> C (p.Asp3253Ala) single nucleotide variant Benign/Likely benign rs140463385 GRCh37 Chromosome 10, 73574728: 73574728
20 CDH23; PSAP NM_022124.5(CDH23): c.9758A> C (p.Asp3253Ala) single nucleotide variant Benign/Likely benign rs140463385 GRCh38 Chromosome 10, 71814971: 71814971
21 CDH23; PSAP NM_022124.5(CDH23): c.9873G> A (p.Thr3291=) single nucleotide variant Benign/Likely benign rs2290021 GRCh37 Chromosome 10, 73574843: 73574843
22 CDH23; PSAP NM_022124.5(CDH23): c.9873G> A (p.Thr3291=) single nucleotide variant Benign/Likely benign rs2290021 GRCh38 Chromosome 10, 71815086: 71815086
23 CDH23; PSAP NM_022124.5(CDH23): c.9903C> T (p.Pro3301=) single nucleotide variant Benign/Likely benign rs55717455 GRCh37 Chromosome 10, 73574873: 73574873
24 CDH23; PSAP NM_022124.5(CDH23): c.9903C> T (p.Pro3301=) single nucleotide variant Benign/Likely benign rs55717455 GRCh38 Chromosome 10, 71815116: 71815116
25 CDH23; PSAP NM_022124.5(CDH23): c.9978C> T (p.Asn3326=) single nucleotide variant Benign rs73277900 GRCh37 Chromosome 10, 73574948: 73574948
26 CDH23; PSAP NM_022124.5(CDH23): c.9978C> T (p.Asn3326=) single nucleotide variant Benign rs73277900 GRCh38 Chromosome 10, 71815191: 71815191
27 CDH23; PSAP NM_002778.3(PSAP): c.1351-14A> G single nucleotide variant Benign/Likely benign rs4747203 GRCh37 Chromosome 10, 73578882: 73578882
28 CDH23; PSAP NM_002778.3(PSAP): c.1351-14A> G single nucleotide variant Benign/Likely benign rs4747203 GRCh38 Chromosome 10, 71819125: 71819125
29 CDH23; PSAP NM_022124.5(CDH23): c.9510+16_9510+22delTCAGGCA deletion Conflicting interpretations of pathogenicity rs149704197 GRCh37 Chromosome 10, 73572385: 73572391
30 CDH23; PSAP NM_022124.5(CDH23): c.9510+16_9510+22delTCAGGCA deletion Conflicting interpretations of pathogenicity rs149704197 GRCh38 Chromosome 10, 71812628: 71812634
31 PSAP NM_002778.3(PSAP): c.1380C> T (p.Pro460=) single nucleotide variant Benign/Likely benign rs1049882 GRCh38 Chromosome 10, 71819082: 71819082
32 PSAP NM_002778.3(PSAP): c.1380C> T (p.Pro460=) single nucleotide variant Benign/Likely benign rs1049882 GRCh37 Chromosome 10, 73578839: 73578839
33 CDH23; PSAP NM_002778.3(PSAP): c.1350+5G> A single nucleotide variant Benign/Likely benign rs11000016 GRCh38 Chromosome 10, 71819460: 71819460
34 CDH23; PSAP NM_002778.3(PSAP): c.1350+5G> A single nucleotide variant Benign/Likely benign rs11000016 GRCh37 Chromosome 10, 73579217: 73579217
35 PSAP NM_002778.3(PSAP): c.-4C> T single nucleotide variant Benign rs2070188 GRCh38 Chromosome 10, 71851225: 71851225
36 PSAP NM_002778.3(PSAP): c.-4C> T single nucleotide variant Benign rs2070188 GRCh37 Chromosome 10, 73610982: 73610982
37 PSAP NM_002778.3(PSAP): c.-10A> G single nucleotide variant Benign/Likely benign rs76455588 GRCh38 Chromosome 10, 71851231: 71851231
38 PSAP NM_002778.3(PSAP): c.-10A> G single nucleotide variant Benign/Likely benign rs76455588 GRCh37 Chromosome 10, 73610988: 73610988
39 PSAP NM_002778.3(PSAP): c.-28A> C single nucleotide variant Likely benign rs375720661 GRCh38 Chromosome 10, 71851249: 71851249
40 PSAP NM_002778.3(PSAP): c.-28A> C single nucleotide variant Likely benign rs375720661 GRCh37 Chromosome 10, 73611006: 73611006
41 CDH23; PSAP NM_022124.5(CDH23): c.9739-12G> A single nucleotide variant Conflicting interpretations of pathogenicity rs200638595 GRCh37 Chromosome 10, 73574697: 73574697
42 CDH23; PSAP NM_022124.5(CDH23): c.9739-12G> A single nucleotide variant Conflicting interpretations of pathogenicity rs200638595 GRCh38 Chromosome 10, 71814940: 71814940
43 CDH23; PSAP NM_022124.5(CDH23): c.*68G> C single nucleotide variant Conflicting interpretations of pathogenicity rs527311705 GRCh37 Chromosome 10, 73575103: 73575103
44 CDH23; PSAP NM_022124.5(CDH23): c.*68G> C single nucleotide variant Conflicting interpretations of pathogenicity rs527311705 GRCh38 Chromosome 10, 71815346: 71815346
45 PSAP NM_002778.3(PSAP): c.*276G> A single nucleotide variant Likely benign rs547409137 GRCh37 Chromosome 10, 73576922: 73576922
46 PSAP NM_002778.3(PSAP): c.*276G> A single nucleotide variant Likely benign rs547409137 GRCh38 Chromosome 10, 71817165: 71817165
47 PSAP NM_002778.3(PSAP): c.*122C> G single nucleotide variant Likely benign rs113284884 GRCh37 Chromosome 10, 73577076: 73577076
48 PSAP NM_002778.3(PSAP): c.*122C> G single nucleotide variant Likely benign rs113284884 GRCh38 Chromosome 10, 71817319: 71817319
49 PSAP NM_002778.3(PSAP): c.*113C> T single nucleotide variant Uncertain significance rs544214520 GRCh37 Chromosome 10, 73577085: 73577085
50 PSAP NM_002778.3(PSAP): c.*113C> T single nucleotide variant Uncertain significance rs544214520 GRCh38 Chromosome 10, 71817328: 71817328

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:

38
# 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
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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