MCID: GLC012
MIFTS: 49

Galactosialidosis

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

Aliases & Classifications for Galactosialidosis

MalaCards integrated aliases for Galactosialidosis:

Name: Galactosialidosis 54 50 24 25 56 71 13 69
Neuraminidase Deficiency with Beta-Galactosidase Deficiency 50 25 56 71
Goldberg Syndrome 50 25 56 71
Ppca Deficiency 50 25 71
Lysosomal Protective Protein Deficiency 25 71
Gsl 50 71
Neuraminidase/beta-Galactosidase Expression 50
Lysosomal Protective Protein Deficiency of 50
Protective Protein/cathepsin a Deficiency 50
Protective Protein Cathepsin a Deficiency 71
Cathepsin a Deficiency of 50
Deficiency of Cathepsin a 25
Cathepsin a Deficiency 71
Cathepsin a 13

Characteristics:

Orphanet epidemiological data:

56
galactosialidosis
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Sweden); Age of onset: All ages;

OMIM:

54
Inheritance:
autosomal recessive


HPO:

32
galactosialidosis:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Galactosialidosis

OMIM : 54
Galactosialidosis is a lysosomal storage disease associated with a combined deficiency of beta-galactosidase (611458) and neuraminidase (608272), secondary to a defect in protective protein/cathepsin A (PPCA). All patients have clinical manifestations typical of a lysosomal disorder, such as coarse facies, cherry red spots, vertebral changes, foam cells in the bone marrow, and vacuolated lymphocytes. Three phenotypic subtypes are recognized. The early infantile form is associated with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. The late infantile type is characterized by hepatosplenomegaly, growth retardation, cardiac involvement, and rare occurrence of neurologic signs. The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, mental retardation, neurologic deterioration, absence of visceromegaly, and long survival. The majority of reported patients belong to the juvenile/adult group and are mainly of Japanese origin (summary by d'Azzo et al., 2001). (256540)

MalaCards based summary : Galactosialidosis, also known as neuraminidase deficiency with beta-galactosidase deficiency, is related to shprintzen-goldberg syndrome and neuroblastoma, and has symptoms including seizures, coarse facial features and intellectual disability. An important gene associated with Galactosialidosis is CTSA (Cathepsin A), and among its related pathways/superpathways are Metabolism and Metabolism of proteins. The drug Krestin has been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and skin.

NIH Rare Diseases : 50 galactosialidosis is an autosomal recessive lysosomal storage disorder caused by mutations in the ctsa gene. it is characterized by coarse facial features, macular cherry-red spots, angiokeratoma (dark red spots on the skin), vertebral deformities, epilepsy, action myoclonus, and ataxia. there are three different types of galactosialidosis: early infantile, late infantile and juvenile/adult. the three forms of galactosialidosis are distinguished by the age at which symptoms develop and the pattern of features. last updated: 5/16/2011

UniProtKB/Swiss-Prot : 71 Galactosialidosis: A lysosomal storage disease associated with a combined deficiency of beta-galactosidase and neuraminidase, secondary to a defect in cathepsin A. All patients have clinical manifestations typical of a lysosomal disorder, such as coarse facies, cherry red spots, vertebral changes, foam cells in the bone marrow, and vacuolated lymphocytes. Three phenotypic subtypes are recognized. The early infantile form is associated with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. The late infantile type is characterized by hepatosplenomegaly, growth retardation, cardiac involvement, and a normal or mildly affected mental state. The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, mental retardation, neurologic deterioration, absence of visceromegaly, and long survival.

Genetics Home Reference : 25 Galactosialidosis is a condition that affects many areas of the body. The three forms of galactosialidosis are distinguished by the age at which symptoms develop and the pattern of features.

Wikipedia : 72 Galactosialidosis is a lysosomal storage disease.This condition is rare and most cases have been in the... more...

Related Diseases for Galactosialidosis

Graphical network of the top 20 diseases related to Galactosialidosis:



Diseases related to Galactosialidosis

Symptoms & Phenotypes for Galactosialidosis

Symptoms via clinical synopsis from OMIM:

54

HEENT:
coarse facies
hearing loss
corneal clouding
conjunctival telangiectases
macular cherry red spot

Skel:
dysostosis multiplex

GI:
usually no organomegaly
occasionally hepatosplenomegaly
vacuolated kupffer cells

Cardiac:
mitral valvular disease
aortic valvular disease

Neuro:
mental retardation
seizures

Growth:
dwarfism

Skin:
widespread hemangiomas

Lab:
em of skin biopsy and peripheral blood lymphocytes shows membrane-bound fibrillogranular inclusions
elevated urine sialyloligosaccharides but no free sialic acid
neuraminidase deficiency
beta-galactosidase deficiency
decreased carboxypeptidase-l/protective protein activity


Clinical features from OMIM:

256540

Human phenotypes related to Galactosialidosis:

56 32 (show all 16)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 56 32 hallmark (90%) Very frequent (99-80%) HP:0001250
2 coarse facial features 56 32 hallmark (90%) Very frequent (99-80%) HP:0000280
3 intellectual disability 56 32 hallmark (90%) Very frequent (99-80%) HP:0001249
4 skeletal dysplasia 56 32 hallmark (90%) Very frequent (99-80%) HP:0002652
5 corneal opacity 56 32 hallmark (90%) Very frequent (99-80%) HP:0007957
6 hearing impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0000365
7 abnormality of the vertebrae 56 32 hallmark (90%) Very frequent (99-80%) HP:0003468
8 cherry red spot of the macula 56 32 hallmark (90%) Very frequent (99-80%) HP:0010729
9 dysostosis multiplex 32 HP:0000943
10 hemangioma 32 HP:0001028
11 hepatosplenomegaly 32 occasional (7.5%) HP:0001433
12 conjunctival telangiectasia 32 HP:0000524
13 opacification of the corneal stroma 32 HP:0007759
14 severe short stature 32 HP:0003510
15 abnormality of the vertebral column 56 Very frequent (99-80%)
16 decreased beta-galactosidase activity 32 HP:0008166

Drugs & Therapeutics for Galactosialidosis

Drugs for Galactosialidosis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Krestin

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions Completed NCT01322165
2 Longitudinal Studies of the Glycoproteinoses Recruiting NCT01891422
3 Characterization of the Patient Population With Galactosialidosis Active, not recruiting NCT01416467

Search NIH Clinical Center for Galactosialidosis

Genetic Tests for Galactosialidosis

Genetic tests related to Galactosialidosis:

id Genetic test Affiliating Genes
1 Galactosialidosis 24 CTSA

Anatomical Context for Galactosialidosis

MalaCards organs/tissues related to Galactosialidosis:

39
Bone, Bone Marrow, Skin, Eye, Brain, Placenta, Retina

Publications for Galactosialidosis

Articles related to Galactosialidosis:

(show top 50) (show all 94)
id Title Authors Year
1
A Turkish case of galactosialidosis with a new homozygous mutation in CTSA gene. ( 28555253 )
2017
2
Galactosialidosis: historic aspects and overview of investigated and emerging treatment options. ( 28603679 )
2017
3
Chemical chaperone treatment for galactosialidosis: Effect of NOEV on I^-galactosidase activities in fibroblasts. ( 26259553 )
2015
4
A Case of Galactosialidosis with Novel Mutations of the Protective Protein/Cathepsin A Gene - Diagnosis Prompted by Trophoblast Vacuolization on Placental Examination. ( 25075748 )
2014
5
Clinical utility of whole-exome sequencing in rare diseases: Galactosialidosis. ( 24769197 )
2014
6
Fundus autofluorescence imaging in a patient with the juvenile form of galactosialidosis. ( 24779613 )
2014
7
Ultrastructural change of ligamentum flavum in galactosialidosis. ( 23989749 )
2013
8
Galactosialidosis: review and analysis of CTSA gene mutations. ( 23915561 )
2013
9
Emphysema in an adult with galactosialidosis linked to a defect in primary elastic fiber assembly. ( 22386972 )
2012
10
Preclinical dose-finding study with a liver-tropic, recombinant AAV-2/8 vector in the mouse model of galactosialidosis. ( 22008912 )
2012
11
Left ventricular "diverticulum" in a patient affected by galactosialidosis. ( 21738533 )
2011
12
Myoclonus and angiokeratomas in adult galactosialidosis. ( 21312277 )
2011
13
Glycan profiling of urine, amniotic fluid and ascitic fluid from galactosialidosis patients reveals novel oligosaccharides with reducing end hexose and aldohexonic acid residues. ( 20546307 )
2010
14
Galactosialidosis presenting as nonimmune fetal hydrops: a case report. ( 19466716 )
2009
15
Juvenile galactosialidosis with attacks of neuropathic pain and absence of sialyloligosacchariduria. ( 19097920 )
2009
16
Galactosialidosis associated with IgA nephropathy: morphological study of renal biopsy. ( 18429828 )
2008
17
A Brazilian galactosialidosis patient given renal transplantation: a case report. ( 18937050 )
2008
18
A case of galactosialidosis with a homozygous Q49R point mutation. ( 18396002 )
2008
19
Elimination of abnormal sialylglycoproteins in fibroblasts with sialidosis and galactosialidosis by normal gene transfer and enzyme replacement. ( 16361247 )
2006
20
Targeting macrophages with baculovirus-produced lysosomal enzymes: implications for enzyme replacement therapy of the glycoprotein storage disorder galactosialidosis. ( 15084520 )
2004
21
Cytochemical and biochemical detection of intracellularly accumulated sialyl glycoconjugates in sialidosis and galactosialidosis fibroblasts with Macckia amurensis. ( 15149881 )
2004
22
Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells. ( 15213228 )
2004
23
A case of galactosialidosis. ( 12932252 )
2003
24
New mutations in two Dutch patients with early infantile galactosialidosis. ( 12649068 )
2003
25
Mitral and aortic valve thickening associated with galactosialidosis: echocardiographic features of a lysosomal storage disease. ( 14536008 )
2003
26
Galactosialidosis: a unique disease with significant clinical implications during perioperative anesthesia management. ( 12818943 )
2003
27
Systemic and neurologic abnormalities distinguish the lysosomal disorders sialidosis and galactosialidosis in mice. ( 12023988 )
2002
28
Functional amelioration of murine galactosialidosis by genetically modified bone marrow hematopoietic progenitor cells. ( 11964280 )
2002
29
A case of adult type galactosialidosis with involvement of peripheral nerves. ( 11081812 )
2000
30
Structural and functional study of K453E mutant protective protein/cathepsin A causing the late infantile form of galactosialidosis. ( 10944848 )
2000
31
Endothelin-1 in the brain of patients with galactosialidosis: its abnormal increase and distribution pattern. ( 10632112 )
2000
32
Stable expression of protective protein/cathepsin A-green fluorescent protein fusion genes in a fibroblastic cell line from a galactosialidosis patient. Model system for revealing the intracellular transport of normal and mutated lysosomal enzymes. ( 10333491 )
1999
33
Vascular pathology in galactosialidosis. ( 10626686 )
1999
34
Early-infantile type of galactosialidosis as a cause of heart failure and neonatal ascites. ( 10399100 )
1999
35
Early-infantile galactosialidosis: prenatal presentation and postnatal follow-up. ( 10377011 )
1999
36
A case with early infantile form of galactosialidosis with unusual haematological findings. ( 10399101 )
1999
37
Anaemia and thrombocytopenia due to haemophagocytosis in a 7-month-old boy with galactosialidosis. ( 9762607 )
1998
38
Unusual pure motor axonal neuropathy in a Burmese family with galactosialidosis. ( 9870214 )
1998
39
Angiokeratoma corporis diffusum associated with galactosialidosis. ( 9693187 )
1998
40
Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis involves its rapid degradation. ( 9480870 )
1998
41
Lack of PPCA expression only partially coincides with lysosomal storage in galactosialidosis mice: indirect evidence for spatial requirement of the catalytic rather than the protective function of PPCA. ( 9736781 )
1998
42
Protective protein/cathepsin A loss in cultured cells derived from an early-infantile form of galactosialidosis patients homozygous for the A1184-G transition (Y395C mutation). ( 9636645 )
1998
43
Correction of murine galactosialidosis by bone marrow-derived macrophages overexpressing human protective protein/cathepsin A under control of the colony-stimulating factor-1 receptor promoter. ( 9843984 )
1998
44
The atomic model of the human protective protein/cathepsin A suggests a structural basis for galactosialidosis. ( 9435242 )
1998
45
Molecular pathology of galactosialidosis in a patient affected with two new frameshift mutations in the cathepsin A/protective protein gene. ( 9603439 )
1998
46
Fetal diagnosis of galactosialidosis (protective protein/cathepsin A deficiency). ( 9437536 )
1997
47
Molecular form and subcellular distribution of acid beta-galactosidase in fibroblasts from patients with GM1 gangliosidosis, Morquio B disease and galactosialidosis. ( 9105659 )
1997
48
Early-infantile galactosialidosis with multiple brain infarctions: morphological, neuropathological and neurochemical findings. ( 9006654 )
1997
49
Early-infantile galactosialidosis: clinical, biochemical, and molecular observations in a new patient. ( 8862621 )
1996
50
Nonimmune hydrops fetalis with galactosialidosis: consequences for family planning. ( 8838767 )
1996

Variations for Galactosialidosis

UniProtKB/Swiss-Prot genetic disease variations for Galactosialidosis:

71 (show all 12)
id Symbol AA change Variation ID SNP ID
1 CTSA p.Gln49Arg VAR_001385 rs137854541
2 CTSA p.Trp65Arg VAR_001386 rs28934603
3 CTSA p.Ser90Leu VAR_001387 rs137854542
4 CTSA p.Tyr249Asn VAR_001388 rs137854544
5 CTSA p.Tyr395Cys VAR_001389 rs137854543
6 CTSA p.Phe440Val VAR_001390 rs137854540
7 CTSA p.Ser51Tyr VAR_063018
8 CTSA p.Val132Met VAR_063019 rs137854545
9 CTSA p.Leu236Pro VAR_063020 rs137854546
10 CTSA p.Met406Thr VAR_063021 rs137854548
11 CTSA p.Gly439Ser VAR_063022 rs137854547
12 CTSA p.Lys453Glu VAR_063023 rs137854549

ClinVar genetic disease variations for Galactosialidosis:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 CTSA NM_000308.3(CTSA): c.746+3A> G single nucleotide variant Pathogenic rs786200859 GRCh37 Chromosome 20, 44521953: 44521953
2 CTSA NM_000308.3(CTSA): c.200A> G (p.Gln67Arg) single nucleotide variant Pathogenic rs137854541 GRCh37 Chromosome 20, 44520353: 44520353
3 CTSA NM_000308.3(CTSA): c.247T> C (p.Trp83Arg) single nucleotide variant Pathogenic rs28934603 GRCh37 Chromosome 20, 44520400: 44520400
4 CTSA NM_000308.3(CTSA): c.323C> T (p.Ser108Leu) single nucleotide variant Pathogenic rs137854542 GRCh37 Chromosome 20, 44520629: 44520629
5 CTSA NM_000308.3(CTSA): c.1238A> G (p.Tyr413Cys) single nucleotide variant Pathogenic rs137854543 GRCh37 Chromosome 20, 44526375: 44526375
6 CTSA NM_000308.3(CTSA): c.799T> A (p.Tyr267Asn) single nucleotide variant Pathogenic rs137854544 GRCh37 Chromosome 20, 44522679: 44522679
7 CTSA NM_000308.3(CTSA): c.448G> A (p.Val150Met) single nucleotide variant Pathogenic rs137854545 GRCh37 Chromosome 20, 44521073: 44521073
8 CTSA NM_000308.3(CTSA): c.284delC (p.Pro95Leufs) deletion Pathogenic rs587779402 GRCh37 Chromosome 20, 44520590: 44520590
9 CTSA NM_000308.3(CTSA): c.887_888delAT (p.Tyr296Cysfs) deletion Pathogenic rs875989777 GRCh37 Chromosome 20, 44523344: 44523345

Expression for Galactosialidosis

Search GEO for disease gene expression data for Galactosialidosis.

Pathways for Galactosialidosis

Pathways related to Galactosialidosis according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
13.51 CTSA GLB1 NEU1 NEU2 NEU3 NEU4
2
Show member pathways
13.27 CTSA GLB1 NEU1 NEU2 NEU3 NEU4
3
Show member pathways
12.62 CTSA GLB1 NEU1 NEU2 NEU3 NEU4
4
Show member pathways
12.04 CTSA GLB1 NEU1 NEU2 NEU3 NEU4
5
Show member pathways
11.72 CTSA GLB1 NEU1 NEU2 NEU3 NEU4
6 11.59 CTSA GLB1 NEU1
7 10.28 GLB1 NEU1 NEU2 NEU3 NEU4

GO Terms for Galactosialidosis

Cellular components related to Galactosialidosis according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 lysosome GO:0005764 9.46 CTSA GLB1 NEU1 NEU4
2 intracellular membrane-bounded organelle GO:0043231 9.35 CTSA GLB1 NEU1 NEU2 NEU3
3 azurophil granule lumen GO:0035578 9.26 CTSA GLB1
4 lysosomal lumen GO:0043202 8.92 CTSA GLB1 NEU1 NEU4

Biological processes related to Galactosialidosis according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 metabolic process GO:0008152 9.77 GLB1 NEU1 NEU2 NEU3 NEU4
2 lipid metabolic process GO:0006629 9.71 NEU1 NEU2 NEU3 NEU4
3 carbohydrate metabolic process GO:0005975 9.65 GLB1 NEU1 NEU2 NEU3 NEU4
4 lipid catabolic process GO:0016042 9.62 NEU1 NEU2 NEU3 NEU4
5 neutrophil degranulation GO:0043312 9.61 CTSA GLB1 NEU1
6 oligosaccharide catabolic process GO:0009313 9.46 NEU1 NEU2 NEU3 NEU4
7 ganglioside catabolic process GO:0006689 9.26 NEU1 NEU2 NEU3 NEU4
8 glycosphingolipid metabolic process GO:0006687 9.1 CTSA GLB1 NEU1 NEU2 NEU3 NEU4

Molecular functions related to Galactosialidosis according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.85 CTSA GLB1 NEU1 NEU2 NEU3 NEU4
2 hydrolase activity, acting on glycosyl bonds GO:0016798 9.72 GLB1 NEU1 NEU2 NEU3 NEU4
3 exo-alpha-(2->6)-sialidase activity GO:0052795 9.56 NEU1 NEU2 NEU3 NEU4
4 exo-alpha-(2->3)-sialidase activity GO:0052794 9.46 NEU1 NEU2 NEU3 NEU4
5 exo-alpha-(2->8)-sialidase activity GO:0052796 9.26 NEU1 NEU2 NEU3 NEU4
6 exo-alpha-sialidase activity GO:0004308 9.1 CTSA GLB1 NEU1 NEU2 NEU3 NEU4

Sources for Galactosialidosis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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