MCID: GCH017
MIFTS: 47

Gaucher Disease, Type Iii

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

Aliases & Classifications for Gaucher Disease, Type Iii

MalaCards integrated aliases for Gaucher Disease, Type Iii:

Name: Gaucher Disease, Type Iii 57 13 38
Gaucher Disease, Subacute Neuronopathic Type 57 12 53 59
Gaucher Disease, Juvenile and Adult, Cerebral 57 12 53
Gaucher Disease, Chronic Neuronopathic Type 57 12 53
Subacute Neuronopathic Gaucher's Disease 29 6 40
Gaucher Disease Type 3 76 53 59
Gd Iii 57 12 75
Cerebral Juvenile and Adult Form of Gaucher Disease 59
Cerebral, Juvenile and Adult, Gaucher Disease 75
Gaucher Disease Chronic Neuronopathic Type 75
Subacute Neuronopathic Gaucher Disease 75
Chronic Neuronopathic Gaucher Disease 59
Gaucher's Disease Type Iii 12
Gaucher Disease Type Ii 75
Gaucher Disease, Type 2 73
Gaucher Disease, Type 3 73
Type 3 Gaucher Disease 55
Gaucher Disease 3 75
Gd 3 53
Gd3 75

Characteristics:

Orphanet epidemiological data:

59
gaucher disease type 3
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Europe); Age of onset: All ages;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
adult onset has been reported
onset usually in childhood (range infancy to late childhood)
subtype 3a comprises myoclonus and dementia
subtype 3b comprises horizontal supranuclear gaze palsy and aggressive systemic disease
subtype 3c comprises cardiovascular calcifications


HPO:

32
gaucher disease, type iii:
Onset and clinical course adult onset phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Gaucher Disease, Type Iii

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 77261Disease definitionGaucher disease type 3 is the subacute neurological form of Gaucher disease (GD; see this term) characterized by progressive encephalopathy and associated with the systemic manifestations (organomegaly, bone involvement, cytopenia) of GD type 1 (see this term).EpidemiologyThe annual incidence of GD is about 1/60,000 and the prevalence is approximately 1/100,000. GD type 3 accounts for 5% of all patients with GD.Clinical descriptionThe clinical presentation is very heterogeneous. Neurological disease appears in childhood or adolescence, a much later onset than in GD type 2 (see this term). Encephalopathy can be the presenting sign of the disease or may occur later in the disease course. Some patients have moderate systemic involvement associated with ophthalmoplegia as the only neurological symptom. For the more severe forms, the neurological signs encountered are variable: supranuclear horizontal ophthalmoplegia, progressive myoclonic epilepsy, cerebellar ataxia, spasticity and dementia. GD type 3 is also associated with the clinical and biological signs of ''systemic'' disease, such as frequent asthenia, growth retardation or delayed puberty, splenomegaly and hepatomegaly. Bone anomalies may also be present and manifest as deformations, osteopenia, which sometimes leads to pathological fractures or vertebral compression, bone infarctions or even aseptic osteonecrosis. Involvement of other organs (rarely symptomatic pulmonary, renal and cardiac) is less common. Pancytopenia is frequent and involves varying degrees of thrombocytopenia (sometimes severe), anemia and, less frequently, leukoneutropenia. Polyclonal hypergammaglobulinemia is often present and is sometimes complicated by monoclonal gammapathy.EtiologyGD type 3 is a lysosomal storage disease caused by a mutation in the GBA gene (1q21) that codes for the lysosomal enzyme, glucocerebrosidase. The deficiency in glucocerebrosidase leads to the accumulation of glucosylceramidase (or beta-glucocerebrosidase) deposits in the cells of the reticuloendothelial system of the liver, spleen and the bone marrow (Gaucher cells).Diagnostic methodsDiagnostic methods involve ultrasound and magnetic resonance imaging (MRI) for initial evaluation and subsequent monitoring of hepatosplenomegaly, radiography and bone scintigraphy to detect bone lesions and complications, osteodensitometry for the evaluation of osteopenia of the lumbar spine and femoral neck, and cardiac ultrasound for the detection of pulmonary arterial hypertension. An increase in certain biological markers that are important both for the initial diagnosis and monitoring with or without treatment, is also observed: chitotriosidase, an angiotensin converting enzyme, ferritin and tartrate-resistant acid phosphatases. Diagnosis can be confirmed by demonstrating a deficit in the enzymatic activity of glucocerebrosidase in circulating leukocytes. In rare cases, genotyping may be of prognostic value: a patient with a homozygous L444P mutation in the GBA gene has a very high risk of developing neurological disease.Genetic counselingTransmission is autosomal recessive.Management and treatmentThe treatment for patients with GD type 3 exhibiting clinically significant non neurological manifestations is enzyme substitution therapy (imiglucerase with marketing authorization (MA) since 1997). It appears to slow progression of the neurological symptoms and is effective against the systemic manifestations.PrognosisIn the absence of treatment, clinical progression leads to death within a few years.Visit the Orphanet disease page for more resources.

MalaCards based summary : Gaucher Disease, Type Iii, also known as gaucher disease, subacute neuronopathic type, is related to gaucher disease, type ii and gaucher's disease, and has symptoms including apnea, muscle rigidity and muscle spasticity. An important gene associated with Gaucher Disease, Type Iii is GBA (Glucosylceramidase Beta), and among its related pathways/superpathways are Sphingolipid metabolism and Lysosome. The drugs Miglustat and 1-Deoxynojirimycin have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and liver, and related phenotypes are ataxia and gait disturbance

OMIM : 57 Gaucher disease type III is the subacute form of neuronopathic Gaucher disease. It has later onset and slower progression compared to the acute form of neuronopathic Gaucher disease, type II. Patterson et al. (1993) suggested that there are 2 phenotypic subgroups of Gaucher disease type III: type IIIA, which is characterized by myoclonus and dementia, and type IIIB, characterized by early onset of isolated horizontal supranuclear gaze palsy and aggressive systemic disease. See also Gaucher disease type IIIC (231005), which is associated with cardiovascular calcifications. (231000)

UniProtKB/Swiss-Prot : 75 Gaucher disease 3: A subacute form of neuronopathic Gaucher disease. It has later onset and slower progression compared to the acute form of neuronopathic Gaucher disease 2.

Disease Ontology : 12 A Gaucher's disease characterized by later onset and slower progession of neurological deterioration compared to type II that has material basis in an autosomal recessive mutation of GBA on chromosome 1q22.

Wikipedia : 76 Gaucher\'s disease or Gaucher disease (/ɡoʊˈʃeɪ/) (GD) is a genetic disorder in which glucocerebroside... more...

Related Diseases for Gaucher Disease, Type Iii

Diseases in the Gaucher's Disease family:

Gaucher Disease, Type I Gaucher Disease, Type Ii
Gaucher Disease, Type Iii Gaucher Disease, Type Iiic
Pseudo-Gaucher Disease

Diseases related to Gaucher Disease, Type Iii via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 35)
# Related Disease Score Top Affiliating Genes
1 gaucher disease, type ii 32.7 GBA PSAP
2 gaucher's disease 28.5 GBA PSAP
3 ocular motor apraxia 11.1
4 gaucher disease, type iiic 11.0
5 melanoma 10.3
6 glioblastoma 10.1
7 breast cancer 9.9
8 neuroblastoma 9.9
9 leukemia 9.9
10 neuronitis 9.9
11 lymphosarcoma 9.9
12 aspartylglucosaminuria 9.8
13 fucosidosis 9.8
14 metachromatic leukodystrophy 9.8
15 adrenoleukodystrophy 9.8
16 mannosidosis 9.8
17 leukodystrophy 9.8
18 central nervous system disease 9.8
19 nervous system disease 9.8
20 lung cancer 9.8
21 enterocolitis 9.8
22 leukemia, chronic myeloid 9.8
23 adult t-cell leukemia 9.8
24 miller fisher syndrome 9.8
25 t-cell leukemia 9.8
26 perinatal necrotizing enterocolitis 9.8
27 type i 9.8
28 hypoxia 9.8
29 endotheliitis 9.8
30 prostatitis 9.7
31 appendicitis 9.7
32 gaucher disease, type i 9.5 GBA PSAP
33 sphingolipidosis 9.4 GBA PSAP
34 niemann-pick disease 9.3 GBA PSAP
35 lipid storage disease 9.2 GBA PSAP

Graphical network of the top 20 diseases related to Gaucher Disease, Type Iii:



Diseases related to Gaucher Disease, Type Iii

Symptoms & Phenotypes for Gaucher Disease, Type Iii

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
ataxia
spastic paraparesis
delayed motor development
subacute neurologic deterioration
more
Abdomen Liver:
hepatomegaly

Hematology:
pancytopenia
thrombocytopenia
gaucher cells in bone marrow

Head And Neck Eyes:
squint
abnormal eye movements
abnormal saccades
supranuclear gaze palsy, horizontal (type iiib)
vertical ocular movements are usually preserved

Laboratory Abnormalities:
decreased beta-glucocerebrosidase protein and activity

AbdomenSpleen:
splenomegaly

Growth Height:
short stature

Neurologic Behavioral Psychiatric Manifestations:
depression

Growth Weight:
decreased weight


Clinical features from OMIM:

231000

Human phenotypes related to Gaucher Disease, Type Iii:

59 32 (show all 44)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 59 32 frequent (33%) Frequent (79-30%) HP:0001251
2 gait disturbance 59 32 frequent (33%) Frequent (79-30%) HP:0001288
3 splenomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001744
4 recurrent respiratory infections 59 32 occasional (7.5%) Occasional (29-5%) HP:0002205
5 hepatomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0002240
6 delayed skeletal maturation 59 32 frequent (33%) Frequent (79-30%) HP:0002750
7 aseptic necrosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0010885
8 proteinuria 59 32 occasional (7.5%) Occasional (29-5%) HP:0000093
9 delayed puberty 59 32 frequent (33%) Frequent (79-30%) HP:0000823
10 fatigue 59 32 hallmark (90%) Very frequent (99-80%) HP:0012378
11 anemia 59 32 frequent (33%) Frequent (79-30%) HP:0001903
12 pancytopenia 59 32 frequent (33%) Frequent (79-30%) HP:0001876
13 pulmonary arterial hypertension 59 32 occasional (7.5%) Occasional (29-5%) HP:0002092
14 generalized myoclonic seizures 59 32 frequent (33%) Frequent (79-30%) HP:0002123
15 strabismus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000486
16 hydrops fetalis 59 32 frequent (33%) Frequent (79-30%) HP:0001789
17 thrombocytopenia 59 32 frequent (33%) Frequent (79-30%) HP:0001873
18 hematuria 59 32 occasional (7.5%) Occasional (29-5%) HP:0000790
19 abnormal myocardium morphology 59 32 occasional (7.5%) Occasional (29-5%) HP:0001637
20 mitral valve calcification 59 32 occasional (7.5%) Occasional (29-5%) HP:0004382
21 dementia 59 32 frequent (33%) Frequent (79-30%) HP:0000726
22 bone pain 59 32 hallmark (90%) Very frequent (99-80%) HP:0002653
23 increased bone mineral density 59 32 hallmark (90%) Very frequent (99-80%) HP:0011001
24 osteolysis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002797
25 encephalopathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0001298
26 ophthalmoplegia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000602
27 aortic valve calcification 59 32 occasional (7.5%) Occasional (29-5%) HP:0004380
28 increased antibody level in blood 59 32 frequent (33%) Frequent (79-30%) HP:0010702
29 interstitial pulmonary abnormality 59 32 occasional (7.5%) Occasional (29-5%) HP:0006530
30 increased susceptibility to fractures 59 32 hallmark (90%) Very frequent (99-80%) HP:0002659
31 pericardial effusion 59 32 occasional (7.5%) Occasional (29-5%) HP:0001698
32 depressivity 32 HP:0000716
33 neurological speech impairment 32 HP:0002167
34 short stature 32 HP:0004322
35 abnormality of the heart valves 59 Occasional (29-5%)
36 myoclonus 32 HP:0001336
37 growth delay 59 Frequent (79-30%)
38 decreased body weight 32 HP:0004325
39 motor delay 32 HP:0001270
40 horizontal supranuclear gaze palsy 32 HP:0007817
41 spastic paraparesis 32 HP:0002313
42 progressive neurologic deterioration 32 HP:0002344
43 decreased beta-glucocerebrosidase protein and activity 32 HP:0003656
44 vascular calcification 32 HP:0004934

UMLS symptoms related to Gaucher Disease, Type Iii:


apnea, muscle rigidity, muscle spasticity, seizures, ataxia, paraparesis, spastic

Drugs & Therapeutics for Gaucher Disease, Type Iii

Drugs for Gaucher Disease, Type Iii (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

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

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 The Effect of Velaglucerase Alfa (Vpriv) on Skeletal Development in Pediatric Gaucher Disease Withdrawn NCT02528617 Phase 4 Velaglucerase alfa
2 Safety and Efficacy of Eliglustat With or Without Imiglucerase in Pediatric Patients With Gaucher Disease (GD) Type 1 and Type 3 Recruiting NCT03485677 Phase 3 Eliglustat GZ385660;Imiglucerase GZ437843
3 OGT 918-006: A Phase I/II Randomized, Controlled Study of OGT 918 in Patients With Neuronopathic Gaucher Disease Completed NCT00041535 Phase 2 OGT 918
4 Efficacy and Safety Study of Velaglucerase Alfa in Children and Adolescents With Type 3 Gaucher Disease Completed NCT01685216 Phase 1, Phase 2
5 GZ/SAR402671 in Combination With Cerezyme in Adult Patients With Gaucher Disease Type 3 Recruiting NCT02843035 Phase 2 GZ402671
6 PEG-Glucocerebrosidase for the Treatment of Gaucher Disease Completed NCT00001410 Phase 1 Lysodase
7 Effects of Enzyme Replacement in Gaucher's Disease Completed NCT00001289
8 Convection-Enhanced Delivery of Glucocerebrosidase to Treat Type 2 Gaucher Disease Completed NCT00244582
9 Study to Evaluate Blood Cell Lines From Patients With Gaucher Disease Completed NCT00351156
10 Eliglustat on Gaucher Disease Type IIIB Enrolling by invitation NCT03519646 Not Applicable Eliglustat

Search NIH Clinical Center for Gaucher Disease, Type Iii

Genetic Tests for Gaucher Disease, Type Iii

Genetic tests related to Gaucher Disease, Type Iii:

# Genetic test Affiliating Genes
1 Subacute Neuronopathic Gaucher's Disease 29 GBA

Anatomical Context for Gaucher Disease, Type Iii

MalaCards organs/tissues related to Gaucher Disease, Type Iii:

41
Bone, Bone Marrow, Liver, Spleen, Lung, Brain, Kidney

Publications for Gaucher Disease, Type Iii

Articles related to Gaucher Disease, Type Iii:

# Title Authors Year
1
Pulmonary involvement in siblings with Gaucher disease type III. ( 22352271 )
2011
2
Bone marrow transplantation as effective treatment of central nervous system disease in globoid cell leukodystrophy, metachromatic leukodystrophy, adrenoleukodystrophy, mannosidosis, fucosidosis, aspartylglucosaminuria, Hurler, Maroteaux-Lamy, and Sly syndromes, and Gaucher disease type III. ( 10226749 )
1999
3
Mutation analysis for prenatal diagnosis and heterozygote detection of Gaucher disease type III (Norrbottnian type). ( 1508850 )
1992

Variations for Gaucher Disease, Type Iii

UniProtKB/Swiss-Prot genetic disease variations for Gaucher Disease, Type Iii:

75
# Symbol AA change Variation ID SNP ID
1 GBA p.Val437Leu VAR_010070
2 GBA p.Thr530Ile VAR_010075 rs78016673

ClinVar genetic disease variations for Gaucher Disease, Type Iii:

6
(show all 24)
# Gene Variation Type Significance SNP ID Assembly Location
1 GBA NM_000157.3(GBA): c.1448T> C (p.Leu483Pro) single nucleotide variant Pathogenic/Likely pathogenic,risk factor rs421016 GRCh37 Chromosome 1, 155205043: 155205043
2 GBA NM_000157.3(GBA): c.1448T> C (p.Leu483Pro) single nucleotide variant Pathogenic/Likely pathogenic,risk factor rs421016 GRCh38 Chromosome 1, 155235252: 155235252
3 GBA NM_001005741.2(GBA): c.1226A> G (p.Asn409Ser) single nucleotide variant Pathogenic/Likely pathogenic,risk factor rs76763715 GRCh37 Chromosome 1, 155205634: 155205634
4 GBA NM_001005741.2(GBA): c.1226A> G (p.Asn409Ser) single nucleotide variant Pathogenic/Likely pathogenic,risk factor rs76763715 GRCh38 Chromosome 1, 155235843: 155235843
5 GBA NM_001005741.2(GBA): c.1297G> T (p.Val433Leu) single nucleotide variant Pathogenic/Likely pathogenic rs80356769 GRCh37 Chromosome 1, 155205563: 155205563
6 GBA NM_001005741.2(GBA): c.1297G> T (p.Val433Leu) single nucleotide variant Pathogenic/Likely pathogenic rs80356769 GRCh38 Chromosome 1, 155235772: 155235772
7 GBA NM_000157.3(GBA): c.1342G> C (p.Asp448His) single nucleotide variant Pathogenic/Likely pathogenic rs1064651 GRCh37 Chromosome 1, 155205518: 155205518
8 GBA NM_000157.3(GBA): c.1342G> C (p.Asp448His) single nucleotide variant Pathogenic/Likely pathogenic rs1064651 GRCh38 Chromosome 1, 155235727: 155235727
9 GBA NM_000157.3(GBA): c.1343A> T (p.Asp448Val) single nucleotide variant Likely pathogenic rs77369218 GRCh37 Chromosome 1, 155205517: 155205517
10 GBA NM_000157.3(GBA): c.1343A> T (p.Asp448Val) single nucleotide variant Likely pathogenic rs77369218 GRCh38 Chromosome 1, 155235726: 155235726
11 GBA NM_000157.3(GBA): c.1504C> T (p.Arg502Cys) single nucleotide variant Pathogenic rs80356771 GRCh37 Chromosome 1, 155204987: 155204987
12 GBA NM_000157.3(GBA): c.1504C> T (p.Arg502Cys) single nucleotide variant Pathogenic rs80356771 GRCh38 Chromosome 1, 155235196: 155235196
13 GBA NM_000157.3(GBA): c.754T> A (p.Phe252Ile) single nucleotide variant Pathogenic rs381737 GRCh37 Chromosome 1, 155207932: 155207932
14 GBA NM_000157.3(GBA): c.754T> A (p.Phe252Ile) single nucleotide variant Pathogenic rs381737 GRCh38 Chromosome 1, 155238141: 155238141
15 GBA NM_000157.3(GBA): c.680A> G (p.Asn227Ser) single nucleotide variant Pathogenic/Likely pathogenic rs364897 GRCh37 Chromosome 1, 155208006: 155208006
16 GBA NM_000157.3(GBA): c.680A> G (p.Asn227Ser) single nucleotide variant Pathogenic/Likely pathogenic rs364897 GRCh38 Chromosome 1, 155238215: 155238215
17 GBA NM_001005741.2(GBA): c.1174C> G (p.Arg392Gly) single nucleotide variant Pathogenic rs121908308 GRCh37 Chromosome 1, 155206086: 155206086
18 GBA NM_001005741.2(GBA): c.1174C> G (p.Arg392Gly) single nucleotide variant Pathogenic rs121908308 GRCh38 Chromosome 1, 155236295: 155236295
19 GBA NM_000157.3(GBA): c.1246G> A (p.Gly416Ser) single nucleotide variant Pathogenic rs121908311 GRCh37 Chromosome 1, 155205614: 155205614
20 GBA NM_000157.3(GBA): c.1246G> A (p.Gly416Ser) single nucleotide variant Pathogenic rs121908311 GRCh38 Chromosome 1, 155235823: 155235823
21 GBA NM_001005741.2(GBA): c.354G> C (p.Lys118Asn) single nucleotide variant Pathogenic rs121908312 GRCh37 Chromosome 1, 155209507: 155209507
22 GBA NM_001005741.2(GBA): c.354G> C (p.Lys118Asn) single nucleotide variant Pathogenic rs121908312 GRCh38 Chromosome 1, 155239716: 155239716
23 GBA NM_000157.3(GBA): c.835C> G (p.Leu279Val) single nucleotide variant Uncertain significance rs1057519020 GRCh38 Chromosome 1, 155237505: 155237505
24 GBA NM_000157.3(GBA): c.835C> G (p.Leu279Val) single nucleotide variant Uncertain significance rs1057519020 GRCh37 Chromosome 1, 155207296: 155207296

Expression for Gaucher Disease, Type Iii

Search GEO for disease gene expression data for Gaucher Disease, Type Iii.

Pathways for Gaucher Disease, Type Iii

Pathways related to Gaucher Disease, Type Iii according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.36 GBA PSAP
2 10.71 GBA PSAP

GO Terms for Gaucher Disease, Type Iii

Cellular components related to Gaucher Disease, Type Iii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosome GO:0005764 9.16 GBA PSAP
2 lysosomal membrane GO:0005765 8.96 GBA PSAP
3 lysosomal lumen GO:0043202 8.62 GBA PSAP

Biological processes related to Gaucher Disease, Type Iii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.16 GBA PSAP
2 glycosphingolipid metabolic process GO:0006687 8.96 GBA PSAP
3 sphingolipid metabolic process GO:0006665 8.62 GBA PSAP

Sources for Gaucher Disease, Type Iii

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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