Gaucher disease type 1

General Information (adopted from Orphanet):

Synonyms, Signs: GD I
GBA deficiency
Glucocerebrosidase deficiency
Non-cerebral juvenile Gaucher disease
Gaucher disease, noncerebral juvenile
Acid beta-glucosidase deficiency
Number of Symptoms 91
OrphanetNr: 77259
OMIM Id: 230800
ICD-10: E75.2
UMLs: C1961835
MeSH:
MedDRA:
Snomed: 62201009

Prevalence, inheritance and age of onset:

Prevalence: <= 0.5 of 100 000 - PMID: 24588457 [IBIS]
Inheritance: Monogenic
Autosomal recessive
- PMID: 24588457 [IBIS]
Age of onset: All ages
- PMID: 24588457 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Cerebral lipidosis with dementia
 -Rare genetic disease
 -Rare neurologic disease
Gaucher disease
 -Rare cardiac disease
 -Rare eye disease
 -Rare genetic disease
Secondary interstitial lung disease in childhood and adulthood associated with a metabolic disease
 -Rare respiratory disease

Comment:

Gaucher disease type I is caused by homozygous or compound heterozygous mutation in the gene encoding acid beta-glucosidase (GBA) (OMIM). Although GD1 is considered a monogenic disorder, there is wide phenotypic heterogeneity not only between patients with the same genetic mutation, but also between twins (PMID:24588457).

Symptom Information: Sort by abundance 

1
 (HPO:0000790) Hematuria Occasional [Orphanet] 12581195 IBIS 106 / 7739
2
 (HPO:0000132) Menorrhagia 25755533 IBIS 40 / 7739
3
 (HPO:0000093) Proteinuria Occasional [Orphanet] 16253723 IBIS 169 / 7739
4
 (HPO:0000421) Epistaxis 11241475; 25755533 IBIS 85 / 7739
5
 (HPO:0000225) Gingival bleeding Occasional [IBIS] Frequent [Orphanet] 17397330 IBIS 28 / 7739
6
 (HPO:0100539) Periorbital edema 11241475 IBIS 8 / 7739
7
 (HPO:0007957) Corneal opacity 25755533 IBIS 84 / 7739
8
 (HPO:0000478) Abnormality of the eye 25755533 IBIS 126 / 7739
9
 (HPO:0001263) Global developmental delay 25755533 IBIS 853 / 7739
10
 (HPO:0012378) Fatigue 25755533 IBIS 50 / 7739
11
 (HPO:0008373) Puberty and gonadal disorders Very frequent [Orphanet] 25755533 IBIS 156 / 7739
12
 (HPO:0000823) Delayed puberty 25755533 IBIS 65 / 7739
13
 (HPO:0001217) Clubbing 25755533 IBIS 39 / 7739
14
 (HPO:0003084) Fractures of the long bones 3385740 IBIS 5 / 7739
15
 (HPO:0004975) Erlenmeyer flask deformity of the femurs 25755533 IBIS 8 / 7739
16
 (HPO:0002653) Bone pain Very frequent [Orphanet] 11241475; 25755533; 24588457; 12919144 IBIS 75 / 7739
17
 (HPO:0005789) Generalized osteosclerosis 25755533 IBIS 10 / 7739
18
 (HPO:0002650) Scoliosis 25755533 IBIS 705 / 7739
19
 (HPO:0011001) Increased bone mineral density Very frequent [Orphanet] 26603719 IBIS 78 / 7739
20
 (HPO:0000939) Osteoporosis 25755533; 26604943 IBIS 129 / 7739
21
 (HPO:0003365) Arthralgia of the hip 3385740; 11241475 IBIS 10 / 7739
22
 (HPO:0002953) Vertebral compression fractures 3385740 IBIS 14 / 7739
23
 (HPO:0005743) Avascular necrosis of the capital femoral epiphysis 3342593; 3385740; 25755533 IBIS 17 / 7739
24
 (HPO:0002750) Delayed skeletal maturation Very frequent [Orphanet] 25755533 IBIS 250 / 7739
25
 (HPO:0002754) Osteomyelitis 11241475; 26604943 IBIS 37 / 7739
26
 (HPO:0010885) Aseptic necrosis Very frequent [Orphanet] 3385740; 25755533; 24588457; 26604942 IBIS 24 / 7739
27
 (HPO:0002797) Osteolysis Very frequent [Orphanet] 25755533 IBIS 68 / 7739
28
 (HPO:0000938) Osteopenia 25755533 IBIS 138 / 7739
29
 (HPO:0002756) Pathologic fracture 25755533; 26604943 IBIS 30 / 7739
30
 (HPO:0000765) Abnormality of the thorax 25755533 IBIS 64 / 7739
31
 (HPO:0001369) Arthritis 3385740; 22046515 IBIS 44 / 7739
32
 (HPO:0002659) Increased susceptibility to fractures Very frequent [Orphanet] 26604942 IBIS 110 / 7739
33
 (HPO:0002758) Osteoarthritis Occasional [Orphanet] 23765538 IBIS 78 / 7739
34
 (HPO:0005146) Cardiac valve calcification 25755533 IBIS 4 / 7739
35
 (HPO:0004349) Reduced bone mineral density Very frequent [Orphanet] 25755533 IBIS 165 / 7739
36
 (HPO:0002808) Kyphosis Frequent [Orphanet] 25755533 IBIS 289 / 7739
37
 (HPO:0001394) Cirrhosis Occasional [Orphanet] 25755533 IBIS 102 / 7739
38
 (HPO:0001744) Splenomegaly Very frequent [Orphanet] 11241475; 25755533; 12919144 IBIS 337 / 7739
39
 (HPO:0002027) Abdominal pain Frequent [Orphanet] 25755533 IBIS 184 / 7739
40
 (HPO:0001081) Cholelithiasis 25755533; 11987238 IBIS 36 / 7739
41
 (HPO:0002014) Diarrhea 25755533 IBIS 225 / 7739
42
 (HPO:0001409) Portal hypertension 25755533 IBIS 39 / 7739
43
 (HPO:0001402) Hepatocellular carcinoma 25755533 IBIS 25 / 7739
44
 (HPO:0001971) Hypersplenism 25755533 IBIS 8 / 7739
45
 (HPO:0001433) Hepatosplenomegaly Frequent [IBIS] 11241475; 25755533; 24588457 IBIS 78 / 7739
46
 (HPO:0002240) Hepatomegaly Very frequent [Orphanet] 11241475; 25755533 IBIS 467 / 7739
47
 (HPO:0001743) Abnormality of the spleen 25755533 IBIS 37 / 7739
48
 (HPO:0001538) Protuberant abdomen 11241475 IBIS 36 / 7739
49
 (HPO:0003270) Abdominal distention 25755533 IBIS 46 / 7739
50
 (HPO:0001395) Hepatic fibrosis 25755533 IBIS 67 / 7739
51
 (HPO:0001508) Failure to thrive 25755533 IBIS 454 / 7739
52
 (HPO:0001510) Growth delay 25755533 IBIS 295 / 7739
53
 (HPO:0007420) Spontaneous hematomas 25755533 IBIS 9 / 7739
54
 (HPO:0000961) Cyanosis 25755533 IBIS 60 / 7739
55
 (HPO:0000967) Petechiae 25755533 IBIS 26 / 7739
56
 (HPO:0000978) Bruising susceptibility Frequent [Orphanet] 25755533 IBIS 123 / 7739
57
 (HPO:0001000) Abnormality of skin pigmentation 12919144 IBIS 105 / 7739
58
 (HPO:0011675) Arrhythmia 25755533 IBIS 226 / 7739
59
 (HPO:0001626) Abnormality of the cardiovascular system 11241475 IBIS 73 / 7739
60
 (HPO:0001279) Syncope 25755533 IBIS 94 / 7739
61
 (HPO:0002092) Pulmonary hypertension Occasional [Orphanet] 25755533 IBIS 109 / 7739
62
 (HPO:0001635) Congestive heart failure 25755533 IBIS 232 / 7739
63
 (HPO:0001892) Abnormal bleeding Frequent [IBIS] 25755533; 24588457 IBIS 85 / 7739
64
 (HPO:0001873) Thrombocytopenia Very frequent [Orphanet] 3385740; 25755533; 24588457; 12919144 IBIS 224 / 7739
65
 (HPO:0001903) Anemia Frequent [IBIS] Frequent [Orphanet] 3385740; 11241475; 25755533; 24588457; 12919144 IBIS 289 / 7739
66
 (HPO:0011869) Abnormal platelet function 25755533 IBIS 12 / 7739
67
 (HPO:0005561) Abnormality of bone marrow cell morphology 25755533 IBIS 11 / 7739
68
 (HPO:0001876) Pancytopenia Frequent [Orphanet] 11241475 IBIS 89 / 7739
69
 (HPO:0001928) Abnormality of coagulation 25755533 IBIS 44 / 7739
70
 (HPO:0006775) Multiple myeloma 25755533 IBIS 10 / 7739
71
 (HPO:0001974) Leukocytosis 25755533 IBIS 33 / 7739
72
 (HPO:0004377) Hematological neoplasm 25755533 IBIS 12 / 7739
73
 (HPO:0010702) Increased antibody level in blood Occasional [Orphanet] 24588457 IBIS 29 / 7739
74
 (HPO:0001882) Leukopenia Occasional [Orphanet] 25755533; 22046515 IBIS 51 / 7739
75
 (HPO:0003656) Decreased beta-glucocerebrosidase protein and activity Very frequent [IBIS] 3385740; 25755533 IBIS 5 / 7739
76
 (HPO:0003281) Increased serum ferritin 24588457 IBIS 32 / 7739
77
 (HPO:0002094) Dyspnea 25755533 IBIS 132 / 7739
78
 (HPO:0006530) Interstitial pulmonary disease Occasional [IBIS] 25755533; 26604942 IBIS 26 / 7739
79
 (HPO:0002205) Recurrent respiratory infections 25755533 IBIS 254 / 7739
80
 (HPO:0002875) Exertional dyspnea 25755533 IBIS 29 / 7739
81
 (HPO:0002716) Lymphadenopathy 25755533 IBIS 129 / 7739
82
 (OMIM) Gaucher cells in bone marrow 25755533 IBIS 5 / 7739
83
 (OMIM) Bone crises 25755533 IBIS 3 / 7739
84
 (OMIM) Increased risk for multiple myeloma 24588457 IBIS 1 / 7739
85
 (HPO:0030157) Flank pain 11241475 IBIS 5 / 7739
86
 (MedDRA:10035060) Pinguecula 25755533 IBIS 4 / 7739
87
 (OMIM) Avascular necrosis of femoral head 24588457 IBIS 2 / 7739
88
 (HPO:0012764) Orthopnea 25755533 IBIS 9 / 7739
89
 (MedDRA:10052274) Hepatopulmonary syndrome 25755533 IBIS 3 / 7739
90
 (MedDRA:10059186) Early satiety 25755533 IBIS 4 / 7739
91
 (MedDRA:10041648) Splenic infarction 25755533 IBIS 3 / 7739

Associated genes:

GBA;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
GBA rs104886460 pathogenic RCV000177098.1
GBA rs1064651 pathogenic RCV000004523.6
GBA rs1135675 pathogenic RCV000004533.4
GBA rs1141814 pathogenic RCV000004565.4
GBA rs121908297 pathogenic RCV000004539.4
GBA rs121908298 pathogenic RCV000004547.4
GBA rs121908299 pathogenic RCV000004550.4
GBA rs121908300 pathogenic RCV000004551.4
GBA rs121908301 pathogenic RCV000004552.4
GBA rs121908302 pathogenic RCV000004556.4
GBA rs121908303 pathogenic RCV000004559.4
GBA rs121908304 pathogenic RCV000004561.4
GBA rs121908305 likely pathogenic RCV000180535.1
GBA rs121908307 pathogenic RCV000004564.4
GBA rs121908309 pathogenic RCV000180538.1
GBA rs121908311 pathogenic RCV000004571.2
GBA rs121908312 pathogenic RCV000004575.3
GBA rs121908314 pathogenic RCV000004578.2
GBA rs2230288 pathogenic RCV000004538.4
GBA rs364897 pathogenic RCV000004557.6
GBA rs381737 pathogenic RCV000004542.4
GBA rs387906315 pathogenic RCV000004543.4
GBA rs397518433 pathogenic RCV000004549.4
GBA rs398123526 pathogenic RCV000180536.1
GBA rs398123527 pathogenic RCV000180534.1
GBA rs398123528 likely pathogenic RCV000173717.1
GBA rs398123529 pathogenic RCV000179354.1
GBA rs398123530 pathogenic RCV000179353.1
GBA rs398123532 pathogenic RCV000179793.1
GBA rs409652 pathogenic RCV000179794.1
GBA rs421016 pathogenic RCV000004511.8
GBA rs61748906 pathogenic RCV000179795.1
GBA rs74500255 pathogenic RCV000004537.4
GBA rs74598136 pathogenic RCV000004568.2
GBA rs75822236 pathogenic RCV000004553.5
GBA rs76539814 pathogenic RCV000004548.6
GBA rs76763715 pathogenic RCV000004515.8
GBA rs77829017 pathogenic RCV000004532.4
GBA rs78396650 pathogenic RCV000004560.4
GBA rs786200979 likely pathogenic RCV000179796.1
GBA rs78973108 pathogenic RCV000180194.1
GBA rs794727708 likely pathogenic RCV000178813.1
GBA rs794727908 likely pathogenic RCV000180196.1
GBA rs79653797 pathogenic RCV000004518.4
GBA rs80356759 pathogenic RCV000004545.4
GBA rs80356768 pathogenic RCV000004554.4
GBA rs80356769 pathogenic RCV000004521.2
GBA rs80356771 pathogenic RCV000004528.5

Additional Information:

Description: (OMIM) Gaucher disease is an autosomal recessive lysosomal storage disorder due to deficient activity of beta-glucocerebrosidase. As a result of this deficiency, there is intracellular accumulation of glucosylceramide (GlcCer, glucosylcerebroside) primarily within cells of mononuclear phagocyte origin, which are ...
Diagnosis OMIM Desnick et al. (1971) demonstrated that both homozygotes and heterozygotes for Gaucher disease could be identified by chemical analysis of the sediment from a 24-hour urine collection. Individual neutral glycosphingolipids were separated by thin-layer chromatography and quantitatively estimated ...
Clinical Description OMIM Type I Gaucher disease usually presents in childhood with hepatosplenomegaly, pancytopenia, and manifestations of bone marrow infiltration by characteristic 'Gaucher cells.' Other features include ocular pingueculae, or nodules, and dermal hyperpigmentation. There is a wide spectrum of clinical ...
Molecular genetics OMIM Tsuji et al. (1987) identified an L444P substitution in the GBA gene (606463.0001) in patients with Gaucher disease types I, II, and III. All 4 patients with type I disease had the mutation as a single allele and ...
Population genetics OMIM Choy et al. (1987) described a method for identification of the carrier state in French Canadians.

In 1982, approximately 20,000 cases of Gaucher disease were reported in the United States. Over two-thirds of these persons were ...