MCID: GM1004
MIFTS: 40

Gm1-Gangliosidosis, Type I

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

Aliases & Classifications for Gm1-Gangliosidosis, Type I

MalaCards integrated aliases for Gm1-Gangliosidosis, Type I:

Name: Gm1-Gangliosidosis, Type I 54 13
Gangliosidosis Generalized Gm1 Type 1 50 71
Beta-Galactosidase-1 Deficiency 50 71
Infantile Gm1 Gangliosidosis 56 29
Gm1 Gangliosidosis Type 1 50 56
Gangliosidosis Generalized Gm1 Infantile Form 50
Gangliosidosis Generalized Gm1 Infantile Type 71
Gangliosidosis, Generalized Gm1, Type 1 69
Beta Galactosidase Deficiency Type 1 50
Beta-Galactosidase Deficiency 69
Gm1-Gangliosidosis Infantile 71
Gangliosidosis Gm1 Infantile 52
Gm1 Gangliosidosis Type I 24
Norman-Landing Disease 56
Glb Deficiency Type 1 50
Gm1-Gangliosidosis 1 71
Gangliosidosis Gm1 69
Glb1 Deficiency 71
Gm1g1 71

Characteristics:

Orphanet epidemiological data:

56
gm1 gangliosidosis type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
death in infancy
allelic to mucopolysaccharidosis ivb


HPO:

32
gm1-gangliosidosis, type i:
Mortality/Aging death in infancy
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Gm1-Gangliosidosis, Type I

OMIM : 54
GM1-Gangliosidosis is an autosomal recessive lysosomal storage disease characterized by accumulation of ganglioside substrates in lysosomes. Clinically, patients show variable degrees of neurodegeneration and skeletal abnormalities. There are 3 main clinical variants categorized by severity and variable residual beta-galactosidase activity. Type I, or infantile form, shows rapid psychomotor deterioration beginning within 6 months of birth, generalized central nervous system involvement, hepatosplenomegaly, facial dysmorphism, macular cherry-red spots, skeletal dysplasia, and early death. Type II, or late-infantile/juvenile form (230600), has onset between 7 months and 3 years, shows generalized central nervous system involvement with psychomotor deterioration, seizures, localized skeletal involvement, and survival into childhood. Hepatosplenomegaly and cherry-red spots are usually not present. Type III, or adult/chronic form (230650), shows onset from 3 to 30 years and is characterized by localized skeletal involvement and localized central nervous system involvement, such as dystonia or gait or speech disturbance. There is an inverse correlation between disease severity and residual enzyme activity (Suzuki et al., 2001). See also Morquio B disease (253010), an allelic disorder with skeletal anomalies and no neurologic involvement. The GM2-gangliosidoses include Tay-Sachs disease (272800) and Sandhoff disease (268800). (230500)

MalaCards based summary : Gm1-Gangliosidosis, Type I, also known as gangliosidosis generalized gm1 type 1, is related to gangliosidosis gm1 and gm1-gangliosidosis, type ii, and has symptoms including scoliosis, hypertrichosis and hepatomegaly. An important gene associated with Gm1-Gangliosidosis, Type I is GLB1 (Galactosidase Beta 1). The drugs Miglustat and 1-Deoxynojirimycin have been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and heart.

NIH Rare Diseases : 50 gm1 gangliosidosis is an inheritedlysosomal storage disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. the condition may be classified into three major types based on the general age that signs and symptoms first appear: classic infantile (type 1); juvenile (type 2); and adult onset or chronic (type 3). although the types differ in severity, their features may overlap significantly. gm1 gangliosidosis is caused by mutations in the glb1 gene and is inherited in an autosomal recessive manner. treatment is currently symptomatic and supportive. last updated: 11/17/2015

UniProtKB/Swiss-Prot : 71 GM1-gangliosidosis 1: An autosomal recessive lysosomal storage disease marked by the accumulation of GM1 gangliosides, glycoproteins and keratan sulfate primarily in neurons of the central nervous system. GM1-gangliosidosis type 1 is characterized by onset within the first three months of life, central nervous system degeneration, coarse facial features, hepatosplenomegaly, skeletal dysmorphology reminiscent of Hurler syndrome, and rapidly progressive psychomotor deterioration. Urinary oligosaccharide levels are high. It leads to death usually between the first and second year of life.

Related Diseases for Gm1-Gangliosidosis, Type I

Diseases in the Gangliosidosis Gm2 family:

Gm1-Gangliosidosis, Type I Gm1-Gangliosidosis, Type Ii
Gm1-Gangliosidosis, Type Iii Gm2-Gangliosidosis, Ab Variant
Gangliosidosis Gm1 Gm2 Gangliosidosis, 0 Variant
Gm2-Gangliosidosis, B, B1, Ab Variant

Diseases related to Gm1-Gangliosidosis, Type I via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 gangliosidosis gm1 11.3
2 gm1-gangliosidosis, type ii 11.1
3 gm1-gangliosidosis, type iii 11.0
4 hydrops fetalis 10.0
5 angiokeratoma 9.9
6 mongolian spot 9.9

Graphical network of the top 20 diseases related to Gm1-Gangliosidosis, Type I:



Diseases related to Gm1-Gangliosidosis, Type I

Symptoms & Phenotypes for Gm1-Gangliosidosis, Type I

Symptoms via clinical synopsis from OMIM:

54

Skeletal- Spine:
scoliosis
kyphosis
hypoplastic vertebral bodies
beaked vertebral bodies

Skin Nails & Hair- Hair:
hypertrichosis

Abdomen- Liver:
hepatomegaly

Head And Neck- Eyes:
hypertelorism
clear cornea
cherry-red spot in half the patients

Head And Neck- Neck:
short neck

Skeletal- Limbs:
joint stiffness

Growth- Height:
dwarfism

Chest- Ribs Sternum Clavicles And Scapulae:
thick ribs

Skin Nails & Hair- Skin:
angiokeratoma corporis diffusum
dermal melanocytosis

Head And Neck- Face:
coarse facies
flat nose
full forehead

Neurologic- Central Nervous System:
mental retardation
cerebral degeneration

Abdomen- Spleen:
splenomegaly

Immunology:
vacuolated lymphocytes

Abdomen- External Features:
inguinal hernia

Head And Neck- Mouth:
gingival hyperplasia

Cardiovascular- Heart:
dilated cardiomyopathy (in a subset of patients)
hypertrophic cardiomyopathy (in a subset of patients)
congestive heart failure (in a subset of patients)
valvular heart disease (in a subset of patients)

Genitourinary- Kidneys:
glomerular epithelial cytoplasmic vacuolization

Metabolic Features:
no mucopolysacchariduria
beta-galactosidase-1 deficiency


Clinical features from OMIM:

230500

Human phenotypes related to Gm1-Gangliosidosis, Type I:

32 (show all 28)
id Description HPO Frequency HPO Source Accession
1 scoliosis 32 HP:0002650
2 hypertrichosis 32 HP:0000998
3 hepatomegaly 32 HP:0002240
4 splenomegaly 32 HP:0001744
5 coarse facial features 32 HP:0000280
6 hypertelorism 32 HP:0000316
7 vacuolated lymphocytes 32 HP:0001922
8 kyphosis 32 HP:0002808
9 frontal bossing 32 HP:0002007
10 hypertrophic cardiomyopathy 32 HP:0001639
11 dilated cardiomyopathy 32 HP:0001644
12 short neck 32 HP:0000470
13 inguinal hernia 32 HP:0000023
14 intellectual disability 32 HP:0001249
15 congestive heart failure 32 HP:0001635
16 joint stiffness 32 HP:0001387
17 hypoplastic vertebral bodies 32 HP:0008479
18 angiokeratoma corporis diffusum 32 HP:0001071
19 cerebral degeneration 32 HP:0007313
20 thickened ribs 32 HP:0000900
21 depressed nasal ridge 32 HP:0000457
22 gingival overgrowth 32 HP:0000212
23 beaking of vertebral bodies 32 HP:0004568
24 cherry red spot of the macula 32 frequent (33%) HP:0010729
25 abnormality of the heart valves 32 HP:0001654
26 severe short stature 32 HP:0003510
27 abnormality of the urinary system 32 HP:0000079
28 decreased beta-galactosidase activity 32 HP:0008166

UMLS symptoms related to Gm1-Gangliosidosis, Type I:


joint stiffness

Drugs & Therapeutics for Gm1-Gangliosidosis, Type I

Drugs for Gm1-Gangliosidosis, Type I (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Miglustat Approved Phase 4 72599-27-0 51634
2
1-Deoxynojirimycin Experimental Phase 4 19130-96-2 1374
3 Anti-HIV Agents Phase 4
4 Anti-Infective Agents Phase 4
5 Anti-Retroviral Agents Phase 4
6 Antiviral Agents Phase 4
7 Cardiac Glycosides Phase 4
8 Glycoside Hydrolase Inhibitors Phase 4
9 Hypoglycemic Agents Phase 4

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Synergistic Enteral Regimen for Treatment of the Gangliosidoses Active, not recruiting NCT02030015 Phase 4 miglustat

Search NIH Clinical Center for Gm1-Gangliosidosis, Type I

Genetic Tests for Gm1-Gangliosidosis, Type I

Genetic tests related to Gm1-Gangliosidosis, Type I:

id Genetic test Affiliating Genes
1 Infantile Gm1 Gangliosidosis 29
2 Gm1 Gangliosidosis Type I 24 GLB1

Anatomical Context for Gm1-Gangliosidosis, Type I

MalaCards organs/tissues related to Gm1-Gangliosidosis, Type I:

39
Brain, Spinal Cord, Heart, Bone, Eye, Skin

Publications for Gm1-Gangliosidosis, Type I

Articles related to Gm1-Gangliosidosis, Type I:

id Title Authors Year
1
GM1-gangliosidosis type I. ( 16942584 )
2006
2
A case of GM1-gangliosidosis type I: glycosphingolipid profiles of urine and transformed lymphocytes and beta-D-galactosidase activities in peripheral lymphocytes, cultured skin fibroblasts and transformed lymphocytes. ( 2117086 )
1990

Variations for Gm1-Gangliosidosis, Type I

UniProtKB/Swiss-Prot genetic disease variations for Gm1-Gangliosidosis, Type I:

71 (show top 50) (show all 51)
id Symbol AA change Variation ID SNP ID
1 GLB1 p.Arg49Cys VAR_003329
2 GLB1 p.Gly123Arg VAR_003331
3 GLB1 p.Arg201Cys VAR_003332
4 GLB1 p.Tyr316Cys VAR_003334
5 GLB1 p.Arg482His VAR_003336
6 GLB1 p.Pro10Leu VAR_008671 rs7637099
7 GLB1 p.Arg59His VAR_008672
8 GLB1 p.Arg121Ser VAR_008675
9 GLB1 p.Arg208Cys VAR_008676
10 GLB1 p.Val240Met VAR_008677
11 GLB1 p.Asp491Asn VAR_008679
12 GLB1 p.Lys578Arg VAR_008682
13 GLB1 p.Tyr591Cys VAR_008684
14 GLB1 p.Tyr591Asn VAR_008685
15 GLB1 p.Arg148Ser VAR_013541
16 GLB1 p.Arg201His VAR_013542
17 GLB1 p.Val216Ala VAR_013544
18 GLB1 p.His281Tyr VAR_013548
19 GLB1 p.Asp332Asn VAR_013549
20 GLB1 p.Gly494Cys VAR_013553
21 GLB1 p.Gly579Asp VAR_013555
22 GLB1 p.Arg59Cys VAR_026129
23 GLB1 p.Arg68Trp VAR_026130
24 GLB1 p.Asp151Tyr VAR_026131
25 GLB1 p.Thr239Met VAR_026132
26 GLB1 p.Gly134Val VAR_037937
27 GLB1 p.Leu162Ser VAR_037940
28 GLB1 p.Asp491Tyr VAR_037943
29 GLB1 p.Pro549Leu VAR_037944
30 GLB1 p.Arg590Cys VAR_037946
31 GLB1 p.Gly272Asp VAR_038346
32 GLB1 p.Met132Thr VAR_062344
33 GLB1 p.Pro136Ser VAR_062345
34 GLB1 p.Asp151Val VAR_062348
35 GLB1 p.Leu173Pro VAR_062349
36 GLB1 p.Gln184Arg VAR_062350
37 GLB1 p.Gly190Asp VAR_062351
38 GLB1 p.Tyr199Cys VAR_062353
39 GLB1 p.Gln255His VAR_062354
40 GLB1 p.Thr329Ile VAR_062357
41 GLB1 p.Asp332Glu VAR_062358
42 GLB1 p.Lys346Asn VAR_062360
43 GLB1 p.Tyr347Cys VAR_062361
44 GLB1 p.Thr420Pro VAR_062364
45 GLB1 p.Leu422Arg VAR_062365
46 GLB1 p.Asp441Asn VAR_062366
47 GLB1 p.Arg442Gln VAR_062367
48 GLB1 p.Pro597Ser VAR_062370
49 GLB1 p.Leu236Pro VAR_074056
50 GLB1 p.Leu337Pro VAR_074061

ClinVar genetic disease variations for Gm1-Gangliosidosis, Type I:

6 (show all 34)
id Gene Variation Type Significance SNP ID Assembly Location
1 GLB1 NM_000404.3(GLB1): c.1369C> T (p.Arg457Ter) single nucleotide variant Pathogenic rs72555359 GRCh37 Chromosome 3, 33058311: 33058311
2 GLB1 NM_000404.2(GLB1): c.1069_1233dup duplication Pathogenic GRCh38 Chromosome 3, 33018562: 33046119
3 GLB1 NM_000404.3(GLB1): c.367G> A (p.Gly123Arg) single nucleotide variant Pathogenic/Likely pathogenic rs28934274 GRCh37 Chromosome 3, 33110341: 33110341
4 GLB1 NM_000404.3(GLB1): c.947A> G (p.Tyr316Cys) single nucleotide variant Pathogenic rs72555361 GRCh37 Chromosome 3, 33093258: 33093258
5 GLB1 NM_000404.3(GLB1): c.1445G> A (p.Arg482His) single nucleotide variant Pathogenic rs72555391 GRCh37 Chromosome 3, 33058235: 33058235
6 GLB1 NM_000404.3(GLB1): c.256_278dup23 (p.Gln95Thrfs) duplication Pathogenic rs587776524 GRCh37 Chromosome 3, 33110430: 33110452
7 GLB1 NM_000404.3(GLB1): c.75+2dupT duplication Pathogenic rs587776525 GRCh37 Chromosome 3, 33138501: 33138501
8 GLB1 NM_000404.3(GLB1): c.622C> T (p.Arg208Cys) single nucleotide variant Pathogenic rs72555366 GRCh37 Chromosome 3, 33099692: 33099692
9 GLB1 NM_000404.3(GLB1): c.176G> A (p.Arg59His) single nucleotide variant Pathogenic rs72555392 GRCh37 Chromosome 3, 33114105: 33114105
10 GLB1 NM_000404.3(GLB1): c.1004C> T (p.Ala335Val) single nucleotide variant Likely pathogenic rs398123347 GRCh37 Chromosome 3, 33087676: 33087676
11 GLB1 NM_000404.3(GLB1): c.1174_1175delCT (p.Leu392Valfs) deletion Pathogenic rs398123348 GRCh37 Chromosome 3, 33063116: 33063117
12 GLB1 NM_000404.3(GLB1): c.1310A> T (p.Asn437Ile) single nucleotide variant Likely pathogenic rs202237232 GRCh37 Chromosome 3, 33059977: 33059977
13 GLB1 NM_000404.3(GLB1): c.1456_1466dupGGTGCATATAT (p.Ile489Metfs) duplication Pathogenic rs398123349 GRCh37 Chromosome 3, 33058214: 33058224
14 GLB1 NM_000404.3(GLB1): c.171C> G (p.Tyr57Ter) single nucleotide variant Pathogenic rs398123350 GRCh37 Chromosome 3, 33114110: 33114110
15 GLB1 NM_000404.3(GLB1): c.1769G> A (p.Arg590His) single nucleotide variant Pathogenic rs398123351 GRCh37 Chromosome 3, 33038802: 33038802
16 GLB1 NM_000404.3(GLB1): c.397-1G> A single nucleotide variant Pathogenic rs398123353 GRCh37 Chromosome 3, 33109783: 33109783
17 GLB1 NM_000404.3(GLB1): c.442C> T (p.Arg148Cys) single nucleotide variant Pathogenic rs192732174 GRCh37 Chromosome 3, 33109737: 33109737
18 GLB1 NM_000404.3(GLB1): c.457+2T> C single nucleotide variant Pathogenic rs398123354 GRCh37 Chromosome 3, 33109720: 33109720
19 GLB1 NM_000404.3(GLB1): c.51dupT (p.Leu18Serfs) duplication Pathogenic rs398123356 GRCh37 Chromosome 3, 33138527: 33138527
20 GLB1 NM_000404.3(GLB1): c.75+1G> C single nucleotide variant Pathogenic rs398123358 GRCh37 Chromosome 3, 33138502: 33138502
21 GLB1 NM_000404.3(GLB1): c.1188dupG (p.Pro397Alafs) duplication Pathogenic rs587779403 GRCh37 Chromosome 3, 33063103: 33063103
22 GLB1 NM_000404.2: c.672_673delAT deletion Pathogenic
23 GLB1 NM_000404.3(GLB1): c.922T> C (p.Phe308Leu) single nucleotide variant Pathogenic rs587779404 GRCh37 Chromosome 3, 33093283: 33093283
24 GLB1 NM_000404.3(GLB1): c.901G> A (p.Ala301Thr) single nucleotide variant Likely pathogenic rs727503954 GRCh38 Chromosome 3, 33051896: 33051896
25 GLB1 NM_000404.3(GLB1): c.1077delA (p.Val360Tyrfs) deletion Pathogenic rs727503952 GRCh37 Chromosome 3, 33065809: 33065809
26 GLB1 NM_000404.3(GLB1): c.1A> C (p.Met1Leu) single nucleotide variant Likely pathogenic rs794726886 GRCh37 Chromosome 3, 33138577: 33138577
27 GLB1 NM_000404.3(GLB1): c.1768C> T (p.Arg590Cys) single nucleotide variant Pathogenic rs794727165 GRCh37 Chromosome 3, 33038803: 33038803
28 GLB1 NM_000404.3(GLB1): c.169delT (p.Tyr57Thrfs) deletion Pathogenic rs794727249 GRCh37 Chromosome 3, 33114112: 33114112
29 GLB1 NM_000404.3(GLB1): c.203G> A (p.Arg68Gln) single nucleotide variant Pathogenic rs572237881 GRCh37 Chromosome 3, 33114078: 33114078
30 GLB1 NM_000404.3(GLB1): c.602G> A (p.Arg201His) single nucleotide variant Pathogenic rs189115557 GRCh37 Chromosome 3, 33099712: 33099712
31 GLB1 NM_000404.3(GLB1): c.809A> G (p.Tyr270Cys) single nucleotide variant Likely pathogenic rs371546950 GRCh37 Chromosome 3, 33093480: 33093480
32 GLB1 NM_000404.3(GLB1): c.1572dupG (p.Trp527Leufs) duplication Pathogenic rs794729217 GRCh38 Chromosome 3, 33014218: 33014218
33 GLB1 NM_000404.3(GLB1): c.808T> G (p.Tyr270Asp) single nucleotide variant Pathogenic rs376663785 GRCh37 Chromosome 3, 33093481: 33093481
34 GLB1 NM_000404.3(GLB1): c.245+1G> A single nucleotide variant Likely pathogenic rs778423653 GRCh37 Chromosome 3, 33114035: 33114035

Expression for Gm1-Gangliosidosis, Type I

Search GEO for disease gene expression data for Gm1-Gangliosidosis, Type I.

Pathways for Gm1-Gangliosidosis, Type I

GO Terms for Gm1-Gangliosidosis, Type I

Sources for Gm1-Gangliosidosis, Type I

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