MCID: CMB020
MIFTS: 30

Combined Saposin Deficiency

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

Aliases & Classifications for Combined Saposin Deficiency

MalaCards integrated aliases for Combined Saposin Deficiency:

Name: Combined Saposin Deficiency 57 75 29 6 73
Combined Sap Deficiency 57 37 13
Prosaposin Deficiency 57 75
Encephalopathy Due to Prosaposin Deficiency 59
Combined Prosaposin Deficiency 59
Prosaposin Deficiency; Psapd 57
Saposin Deficiency, Combined 40
Prosaposin 13
Psapd 57
Csapd 75

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


Classifications:



Summaries for Combined Saposin Deficiency

UniProtKB/Swiss-Prot : 75 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 encephalopathy due to prosaposin deficiency and trehalase deficiency, and has symptoms including muscular fasciculation and myoclonus. 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 splenomegaly and hepatomegaly

Description 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:

# Related Disease Score Top Affiliating Genes
1 encephalopathy due to prosaposin deficiency 11.3
2 trehalase deficiency 9.2 CDH23 PSAP
3 retinitis pigmentosa 9.0 CDH23 PSAP

Symptoms & Phenotypes for Combined Saposin Deficiency

Symptoms via clinical synopsis from OMIM:

57
AbdomenSpleen:
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

Human phenotypes related to Combined Saposin Deficiency:

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

UMLS symptoms related to Combined Saposin Deficiency:


muscular fasciculation, myoclonus

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, Skin, Testis

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
Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient mice. ( 18673548 )
2008
4
Neurolysosomal pathology in human prosaposin deficiency suggests essential neurotrophic function of prosaposin. ( 17024494 )
2007
5
Prosaposin deficiency -- a rarely diagnosed, rapidly progressing, neonatal neurovisceral lipid storage disease. Report of a further patient. ( 15944902 )
2005
6
Seminolipid and its precursor/degradative product, galactosylalkylacylglycerol, in the testis of saposin A- and prosaposin-deficient mice. ( 12810822 )
2003
7
Quantification of mRNAs encoding proteins of the glycosphingolipid catabolism in mouse models of GM2 gangliosidoses and sphingolipid activator protein precursor (prosaposin) deficiency. ( 11068181 )
2000
8
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
9
Metabolism of GM1 ganglioside in cultured skin fibroblasts: anomalies in gangliosidoses, sialidoses, and sphingolipid activator protein (SAP, saposin) 1 and prosaposin deficient disorders. ( 1634229 )
1992

Variations for Combined Saposin Deficiency

ClinVar genetic disease variations for Combined Saposin Deficiency:

6
(show top 50) (show all 168)
# Gene Variation Type Significance SNP ID Assembly Location
1 PSAP NM_001042465.2(PSAP): c.722G> C (p.Cys241Ser) single nucleotide variant Pathogenic rs121918104 GRCh37 Chromosome 10, 73585649: 73585649
2 PSAP NM_001042465.2(PSAP): c.722G> C (p.Cys241Ser) single nucleotide variant Pathogenic rs121918104 GRCh38 Chromosome 10, 71825892: 71825892
3 PSAP NM_001042465.2(PSAP): c.1A> T (p.Met1Leu) single nucleotide variant Pathogenic rs121918106 GRCh37 Chromosome 10, 73610978: 73610978
4 PSAP NM_001042465.2(PSAP): c.1A> T (p.Met1Leu) single nucleotide variant Pathogenic rs121918106 GRCh38 Chromosome 10, 71851221: 71851221
5 PSAP PSAP, 1-BP DEL, 803G deletion Pathogenic
6 PSAP PSAP, IVS9AS, A-G, -2 single nucleotide variant Pathogenic
7 CDH23; PSAP NM_022124.5(CDH23): c.9510+13C> T single nucleotide variant Benign/Likely benign rs183692794 GRCh37 Chromosome 10, 73572379: 73572379
8 CDH23; PSAP NM_022124.5(CDH23): c.9510+13C> T single nucleotide variant Benign/Likely benign rs183692794 GRCh38 Chromosome 10, 71812622: 71812622
9 CDH23; PSAP NM_022124.5(CDH23): c.9629T> C (p.Ile3210Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs144688588 GRCh37 Chromosome 10, 73572643: 73572643
10 CDH23; PSAP NM_022124.5(CDH23): c.9629T> C (p.Ile3210Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs144688588 GRCh38 Chromosome 10, 71812886: 71812886
11 CDH23; PSAP NM_022124.5(CDH23): c.10026C> T (p.Asp3342=) single nucleotide variant Conflicting interpretations of pathogenicity rs377118941 GRCh37 Chromosome 10, 73574996: 73574996
12 CDH23; PSAP NM_022124.5(CDH23): c.10026C> T (p.Asp3342=) single nucleotide variant Conflicting interpretations of pathogenicity rs377118941 GRCh38 Chromosome 10, 71815239: 71815239
13 PSAP NM_002778.3(PSAP): c.1380C> T (p.Pro460=) single nucleotide variant Likely benign rs1049882 GRCh38 Chromosome 10, 71819082: 71819082
14 PSAP NM_002778.3(PSAP): c.1380C> T (p.Pro460=) single nucleotide variant Likely benign rs1049882 GRCh37 Chromosome 10, 73578839: 73578839
15 CDH23; PSAP NM_002778.3(PSAP): c.1350+5G> A single nucleotide variant Benign/Likely benign rs11000016 GRCh38 Chromosome 10, 71819460: 71819460
16 CDH23; PSAP NM_002778.3(PSAP): c.1350+5G> A single nucleotide variant Benign/Likely benign rs11000016 GRCh37 Chromosome 10, 73579217: 73579217
17 PSAP NM_002778.3(PSAP): c.-4C> T single nucleotide variant Benign rs2070188 GRCh38 Chromosome 10, 71851225: 71851225
18 PSAP NM_002778.3(PSAP): c.-4C> T single nucleotide variant Benign rs2070188 GRCh37 Chromosome 10, 73610982: 73610982
19 PSAP NM_002778.3(PSAP): c.-10A> G single nucleotide variant Likely benign rs76455588 GRCh38 Chromosome 10, 71851231: 71851231
20 PSAP NM_002778.3(PSAP): c.-10A> G single nucleotide variant Likely benign rs76455588 GRCh37 Chromosome 10, 73610988: 73610988
21 PSAP NM_002778.3(PSAP): c.-28A> C single nucleotide variant Likely benign rs375720661 GRCh38 Chromosome 10, 71851249: 71851249
22 PSAP NM_002778.3(PSAP): c.-28A> C single nucleotide variant Likely benign rs375720661 GRCh37 Chromosome 10, 73611006: 73611006
23 CDH23; PSAP NM_022124.5(CDH23): c.9739-12G> A single nucleotide variant Conflicting interpretations of pathogenicity rs200638595 GRCh38 Chromosome 10, 71814940: 71814940
24 CDH23; PSAP NM_022124.5(CDH23): c.9739-12G> A single nucleotide variant Conflicting interpretations of pathogenicity rs200638595 GRCh37 Chromosome 10, 73574697: 73574697
25 CDH23; PSAP NM_022124.5(CDH23): c.*68G> C single nucleotide variant Conflicting interpretations of pathogenicity rs527311705 GRCh37 Chromosome 10, 73575103: 73575103
26 CDH23; PSAP NM_022124.5(CDH23): c.*68G> C single nucleotide variant Conflicting interpretations of pathogenicity rs527311705 GRCh38 Chromosome 10, 71815346: 71815346
27 PSAP NM_002778.3(PSAP): c.*276G> A single nucleotide variant Likely benign rs547409137 GRCh37 Chromosome 10, 73576922: 73576922
28 PSAP NM_002778.3(PSAP): c.*276G> A single nucleotide variant Likely benign rs547409137 GRCh38 Chromosome 10, 71817165: 71817165
29 PSAP NM_002778.3(PSAP): c.*122C> G single nucleotide variant Likely benign rs113284884 GRCh37 Chromosome 10, 73577076: 73577076
30 PSAP NM_002778.3(PSAP): c.*122C> G single nucleotide variant Likely benign rs113284884 GRCh38 Chromosome 10, 71817319: 71817319
31 PSAP NM_002778.3(PSAP): c.*113C> T single nucleotide variant Uncertain significance rs544214520 GRCh37 Chromosome 10, 73577085: 73577085
32 PSAP NM_002778.3(PSAP): c.*113C> T single nucleotide variant Uncertain significance rs544214520 GRCh38 Chromosome 10, 71817328: 71817328
33 PSAP NM_002778.3(PSAP): c.*73C> T single nucleotide variant Likely benign rs541692197 GRCh37 Chromosome 10, 73577125: 73577125
34 PSAP NM_002778.3(PSAP): c.*73C> T single nucleotide variant Likely benign rs541692197 GRCh38 Chromosome 10, 71817368: 71817368
35 PSAP NM_002778.3(PSAP): c.1476T> C (p.Thr492=) single nucleotide variant Likely benign rs139178900 GRCh37 Chromosome 10, 73578437: 73578437
36 PSAP NM_002778.3(PSAP): c.1476T> C (p.Thr492=) single nucleotide variant Likely benign rs139178900 GRCh38 Chromosome 10, 71818680: 71818680
37 PSAP NM_002778.3(PSAP): c.1432-4A> G single nucleotide variant Uncertain significance rs775086571 GRCh37 Chromosome 10, 73578485: 73578485
38 PSAP NM_002778.3(PSAP): c.1432-4A> G single nucleotide variant Uncertain significance rs775086571 GRCh38 Chromosome 10, 71818728: 71818728
39 PSAP NM_002778.3(PSAP): c.1172C> T (p.Thr391Met) single nucleotide variant Uncertain significance rs202125074 GRCh37 Chromosome 10, 73579491: 73579491
40 PSAP NM_002778.3(PSAP): c.1172C> T (p.Thr391Met) single nucleotide variant Uncertain significance rs202125074 GRCh38 Chromosome 10, 71819734: 71819734
41 PSAP NM_002778.3(PSAP): c.1056C> T (p.Ser352=) single nucleotide variant Likely benign rs138328594 GRCh37 Chromosome 10, 73579607: 73579607
42 PSAP NM_002778.3(PSAP): c.1056C> T (p.Ser352=) single nucleotide variant Likely benign rs138328594 GRCh38 Chromosome 10, 71819850: 71819850
43 PSAP NM_002778.3(PSAP): c.911A> G (p.Lys304Arg) single nucleotide variant Uncertain significance rs757553906 GRCh37 Chromosome 10, 73580091: 73580091
44 PSAP NM_002778.3(PSAP): c.911A> G (p.Lys304Arg) single nucleotide variant Uncertain significance rs757553906 GRCh38 Chromosome 10, 71820334: 71820334
45 PSAP NM_002778.3(PSAP): c.380G> A (p.Arg127His) single nucleotide variant Uncertain significance rs886047151 GRCh38 Chromosome 10, 71829073: 71829073
46 PSAP NM_002778.3(PSAP): c.380G> A (p.Arg127His) single nucleotide variant Uncertain significance rs886047151 GRCh37 Chromosome 10, 73588830: 73588830
47 PSAP NM_002778.3(PSAP): c.336C> T (p.Ser112=) single nucleotide variant Likely benign rs370977178 GRCh38 Chromosome 10, 71831165: 71831165
48 PSAP NM_002778.3(PSAP): c.336C> T (p.Ser112=) single nucleotide variant Likely benign rs370977178 GRCh37 Chromosome 10, 73590922: 73590922
49 PSAP NM_002778.3(PSAP): c.174+9C> T single nucleotide variant Likely benign rs141133813 GRCh37 Chromosome 10, 73594120: 73594120
50 PSAP NM_002778.3(PSAP): c.174+9C> T single nucleotide variant Likely benign rs141133813 GRCh38 Chromosome 10, 71834363: 71834363

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 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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