Gaucher disease type 3

General Information (adopted from Orphanet):

Synonyms, Signs: GD III
Gaucher disease, type IIIB, included
Chronic neuronopathic Gaucher disease
Cerebral juvenile and adult form of Gaucher disease
Gaucher disease, norrbottnian type, included
Gaucher disease, juvenile and adult, cerebral Gaucher disease, type IIIA, included
Gaucher disease, chronic neuronopathic type
Gaucher disease, subacute neuronopathic type
Number of Symptoms 120
OrphanetNr: 77261
OMIM Id: 231000
ICD-10: E75.2
UMLs: C0268251
MeSH:
MedDRA:
Snomed: 5963005

Prevalence, inheritance and age of onset:

Prevalence: < 0.1 of 100 000
Inheritance: Autosomal recessive
25755533 [IBIS]
Age of onset: Childhood
Adolescence
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
Neurometabolic disease
 -Rare genetic disease
 -Rare neurologic disease
Secondary interstitial lung disease specific to childhood associated with a metabolic disease
 -Rare respiratory disease
Sphingolipidosis with epilepsy
 -Rare neurologic disease

Comment:

Gaucher disease type III is caused by homozygous or compound heterozygous mutation in the gene encoding acid beta-glucosidase (GBA) (OMIM). Type 3 Gaucher disease (GD) is the chronic neuronopathic form of GD and has a later onset than GD2. However, GD3 may have onset before age two years with slow progression. GD3 is characterized by a milder neurological involvement compared to that seen in GD2, in addition to the visceral and bone marrow involvement as in GD1. (PMID:25755533)

Symptom Information: Sort by abundance 

1
 (HPO:0002795) Functional respiratory abnormality 25219293; 20307947 IBIS 13 / 7739
2
 (HPO:0000132) Menorrhagia 25755533 IBIS 40 / 7739
3
 (HPO:0000421) Epistaxis 25755533 IBIS 85 / 7739
4
 (HPO:0000514) Slow saccadic eye movements 25755533 IBIS 21 / 7739
5
 (HPO:0000486) Strabismus Frequent [IBIS] Very frequent [Orphanet] 25755533; 4003050; 25859481; 20307947; 19481486 IBIS 576 / 7739
6
 (HPO:0007957) Corneal opacity 25755533; 19481486 IBIS 84 / 7739
7
 (HPO:0000605) Supranuclear gaze palsy 25755533 IBIS 16 / 7739
8
 (HPO:0000479) Abnormality of the retina 4003050 IBIS 74 / 7739
9
 (HPO:0000545) Myopia 4003050 IBIS 286 / 7739
10
 (HPO:0000639) Nystagmus 19481486 IBIS 555 / 7739
11
 (HPO:0000570) Abnormality of saccadic eye movements 25755533; 20307947 IBIS 12 / 7739
12
 (HPO:0007817) Horizontal supranuclear gaze palsy 24588457; 24588457; 8413956 IBIS 3 / 7739
13
 (HPO:0000602) Ophthalmoplegia 20307947 IBIS 56 / 7739
14
 (HPO:0000657) Oculomotor apraxia Frequent [IBIS] 25755533; 4003050; 25219293; 20307947 IBIS 54 / 7739
15
 (HPO:0000496) Abnormality of eye movement Very frequent [Orphanet] 25755533; 25219293 IBIS 79 / 7739
16
 (HPO:0002063) Rigidity 25755533 IBIS 92 / 7739
17
 (HPO:0001288) Gait disturbance Frequent [Orphanet] 20307947 IBIS 318 / 7739
18
 (HPO:0002123) Generalized myoclonic seizures 24588457; 8780099 IBIS 62 / 7739
19
 (HPO:0012378) Fatigue 25755533 IBIS 50 / 7739
20
 (HPO:0001276) Hypertonia Frequent [Orphanet] 25755533 IBIS 317 / 7739
21
 (HPO:0002080) Intention tremor 25219293 IBIS 44 / 7739
22
 (HPO:0012323) Sleep myoclonus 25219293 IBIS 1 / 7739
23
 (HPO:0001249) Intellectual disability 20307947 IBIS 1089 / 7739
24
 (HPO:0001250) Seizures Frequent [Orphanet] 25755533; 25859481; 20307947; 19481486 IBIS 1245 / 7739
25
 (HPO:0002344) Progressive neurologic deterioration 25755533 IBIS 27 / 7739
26
 (HPO:0007256) Abnormal pyramidal signs 20307947 IBIS 116 / 7739
27
 (HPO:0001337) Tremor 20307947 IBIS 200 / 7739
28
 (HPO:0000716) Depression 20307947 IBIS 99 / 7739
29
 (HPO:0002395) Lower limb hyperreflexia 25219293 IBIS 26 / 7739
30
 (HPO:0002015) Dysphagia 25755533; 20307947 IBIS 301 / 7739
31
 (HPO:0001263) Global developmental delay 25755533; 25219293; 19481486; 19481486 IBIS 853 / 7739
32
 (HPO:0002073) Progressive cerebellar ataxia 25219293; 20307947 IBIS 27 / 7739
33
 (HPO:0001268) Mental deterioration 24588457 IBIS 88 / 7739
34
 (HPO:0000718) Aggressive behavior 25859481; 20307947 IBIS 109 / 7739
35
 (HPO:0001332) Dystonia 20307947 IBIS 197 / 7739
36
 (HPO:0001336) Myoclonus 25755533; 8413956; 20307947; 19481486 IBIS 115 / 7739
37
 (HPO:0002179) Opisthotonus 25755533 IBIS 35 / 7739
38
 (HPO:0002069) Generalized tonic-clonic seizures 25219293; 20307947 IBIS 96 / 7739
39
 (HPO:0000726) Dementia 25755533; 8413956; 25859481 IBIS 131 / 7739
40
 (HPO:0002355) Difficulty walking 20307947 IBIS 61 / 7739
41
 (HPO:0001251) Ataxia 25755533 IBIS 413 / 7739
42
 (HPO:0010885) Aseptic necrosis Very frequent [Orphanet] 20307947 IBIS 24 / 7739
43
 (HPO:0002653) Bone pain Very frequent [Orphanet] 25755533; 26693402 IBIS 75 / 7739
44
 (HPO:0005743) Avascular necrosis of the capital femoral epiphysis 25755533 IBIS 17 / 7739
45
 (HPO:0002808) Kyphosis 25755533; 24588457 IBIS 289 / 7739
46
 (HPO:0002659) Increased susceptibility to fractures Very frequent [Orphanet] 25219293 IBIS 110 / 7739
47
 (HPO:0000766) Abnormality of the sternum 20307947 IBIS 31 / 7739
48
 (HPO:0002797) Osteolysis Very frequent [Orphanet] 25755533; 26693402 IBIS 68 / 7739
49
 (HPO:0004975) Erlenmeyer flask deformity of the femurs 25755533; 26693402 IBIS 8 / 7739
50
 (HPO:0002942) Thoracic kyphosis 20307947 IBIS 14 / 7739
51
 (HPO:0000938) Osteopenia 25755533; 26693402; 20307947 IBIS 138 / 7739
52
 (HPO:0005146) Cardiac valve calcification 25755533; 19481486 IBIS 4 / 7739
53
 (HPO:0005789) Generalized osteosclerosis 25755533 IBIS 10 / 7739
54
 (HPO:0000939) Osteoporosis 25219293 IBIS 129 / 7739
55
 (HPO:0002953) Vertebral compression fractures 20307947 IBIS 14 / 7739
56
 (HPO:0000765) Abnormality of the thorax 25755533 IBIS 64 / 7739
57
 (HPO:0002650) Scoliosis 25755533 IBIS 705 / 7739
58
 (HPO:0001217) Clubbing 25755533 IBIS 39 / 7739
59
 (HPO:0002240) Hepatomegaly Very frequent [Orphanet] 25755533 IBIS 467 / 7739
60
 (HPO:0002024) Malabsorption 25219293 IBIS 142 / 7739
61
 (HPO:0003270) Abdominal distention 25219293 IBIS 46 / 7739
62
 (HPO:0002027) Abdominal pain 25755533 IBIS 184 / 7739
63
 (HPO:0001081) Cholelithiasis 25755533 IBIS 36 / 7739
64
 (HPO:0002013) Vomiting 25219293 IBIS 191 / 7739
65
 (HPO:0002243) Protein-losing enteropathy 25219293 IBIS 8 / 7739
66
 (HPO:0001402) Hepatocellular carcinoma 25755533 IBIS 25 / 7739
67
 (HPO:0001744) Splenomegaly Very frequent [Orphanet] 25755533; 20307947 IBIS 337 / 7739
68
 (HPO:0001743) Abnormality of the spleen 25755533 IBIS 37 / 7739
69
 (HPO:0001394) Cirrhosis 25755533 IBIS 102 / 7739
70
 (HPO:0001409) Portal hypertension 25755533 IBIS 39 / 7739
71
 (HPO:0001541) Ascites 25219293 IBIS 94 / 7739
72
 (HPO:0001433) Hepatosplenomegaly Frequent [IBIS] 25755533; 24588457; 25219293; 25859481; 19481486 IBIS 78 / 7739
73
 (HPO:0002014) Diarrhea 25755533; 25219293 IBIS 225 / 7739
74
 (HPO:0001510) Growth delay 25755533; 24588457; 25219293 IBIS 295 / 7739
75
 (HPO:0004322) Short stature 8413956 IBIS 1232 / 7739
76
 (HPO:0004325) Decreased body weight Frequent [Orphanet] 8413956 IBIS 492 / 7739
77
 (HPO:0001508) Failure to thrive 25755533 IBIS 454 / 7739
78
 (HPO:0000980) Pallor 25859481 IBIS 52 / 7739
79
 (HPO:0000967) Petechiae 25755533 IBIS 26 / 7739
80
 (HPO:0007420) Spontaneous hematomas 25755533 IBIS 9 / 7739
81
 (HPO:0000961) Cyanosis 25755533 IBIS 60 / 7739
82
 (HPO:0011675) Arrhythmia 25755533 IBIS 226 / 7739
83
 (HPO:0001279) Syncope 25755533 IBIS 94 / 7739
84
 (HPO:0001635) Congestive heart failure 25755533 IBIS 232 / 7739
85
 (HPO:0002092) Pulmonary hypertension Occasional [Orphanet] 25755533 IBIS 109 / 7739
86
 (HPO:0100724) Hypercoagulability 25219293 IBIS 15 / 7739
87
 (HPO:0001882) Leukopenia Frequent [Orphanet] 25755533; 7160406 IBIS 51 / 7739
88
 (HPO:0001888) Lymphopenia 20307947 IBIS 43 / 7739
89
 (HPO:0001903) Anemia Frequent [IBIS] Frequent [Orphanet] 25755533; 7160406; 25219293; 20307947 IBIS 289 / 7739
90
 (HPO:0006775) Multiple myeloma 25755533 IBIS 10 / 7739
91
 (HPO:0001892) Abnormal bleeding 25755533; 24588457 IBIS 85 / 7739
92
 (HPO:0004377) Hematological neoplasm 25755533 IBIS 12 / 7739
93
 (HPO:0001873) Thrombocytopenia Frequent [IBIS] Frequent [Orphanet] 25755533; 24588457; 7160406; 25219293; 20307947 IBIS 224 / 7739
94
 (HPO:0001977) Abnormal thrombosis 25219293 IBIS 11 / 7739
95
 (HPO:0003656) Decreased beta-glucocerebrosidase protein and activity Very frequent [IBIS] 25755533; 25219293 IBIS 5 / 7739
96
 (HPO:0003111) Abnormality of ion homeostasis 25219293 IBIS 1 / 7739
97
 (HPO:0000969) Edema 25219293 IBIS 117 / 7739
98
 (HPO:0003073) Hypoalbuminemia 25219293 IBIS 40 / 7739
99
 (HPO:0002206) Pulmonary fibrosis 25219293 IBIS 51 / 7739
100
 (HPO:0002875) Exertional dyspnea 25755533 IBIS 29 / 7739
101
 (HPO:0002205) Recurrent respiratory infections Occasional [Orphanet] 25755533 IBIS 254 / 7739
102
 (HPO:0002091) Restrictive ventilatory defect Occasional [Orphanet] 25219293; 20307947 IBIS 46 / 7739
103
 (HPO:0002094) Dyspnea 25755533; 25219293 IBIS 132 / 7739
104
 (HPO:0006530) Interstitial pulmonary disease 25219293; 20307947 IBIS 26 / 7739
105
 (HPO:0002716) Lymphadenopathy 25755533; 25219293 IBIS 129 / 7739
106
 (HPO:0001283) Bulbar palsy 25755533 IBIS 31 / 7739
107
 (HPO:0000238) Hydrocephalus 19481486 IBIS 278 / 7739
108
 (HPO:0002180) Neurodegeneration 25219293 IBIS 31 / 7739
109
 (MedDRA:10047924) Wheezing 25219293 IBIS 8 / 7739
110
 (MedDRA:10052274) Hepatopulmonary syndrome 25755533 IBIS 3 / 7739
111
 (OMIM) Gaucher cells in bone marrow 25755533 IBIS 5 / 7739
112
 (MedDRA:10064833) Retinal infiltrates 4003050 IBIS 1 / 7739
113
 (MedDRA:10067015) Retroperitoneal lymphadenopathy 25219293 IBIS 1 / 7739
114
 (HPO:0012764) Orthopnea 25755533 IBIS 9 / 7739
115
 (MedDRA:10035060) Pinguecula 25755533 IBIS 4 / 7739
116
 (HPO:0002446) Astrocytosis 25219293 IBIS 7 / 7739
117
 (MedDRA:10041648) Splenic infarction 25755533 IBIS 3 / 7739
118
 (MedDRA:10059186) Early satiety 25755533 IBIS 4 / 7739
119
 (OMIM) Bone crises 25755533 IBIS 3 / 7739
120
 (HPO:0040121) Abnormality of the acoustic reflex 11521209 IBIS 1 / 7739

Associated genes:

GBA;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
GBA rs1064651 pathogenic RCV000004525.5
GBA rs1135675 pathogenic RCV000004535.4
GBA rs121908308 pathogenic RCV000004567.4
GBA rs121908311 pathogenic RCV000004572.2
GBA rs121908312 pathogenic RCV000004576.2
GBA rs364897 pathogenic RCV000004558.4
GBA rs367968666 pathogenic RCV000004581.2
GBA rs381737 pathogenic RCV000004540.4
GBA rs421016 pathogenic RCV000004510.9
GBA rs77369218 pathogenic RCV000004527.2
GBA rs80356769 pathogenic RCV000004520.2
GBA rs80356771 pathogenic RCV000004530.4

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM Herrlin and Hillborg (1962) reported a pedigree with juvenile Gaucher disease and neurologic signs.

Miller et al. (1973) described Gaucher disease with neurologic manifestations in 3 adult sibs. Features included seizures and decreased beta-glucocerebrosidase activity. ...
Molecular genetics OMIM Dahl et al. (1990) showed that the Norrbottnian form of Gaucher disease is caused by homozygosity for the leu444-to-pro (L444P; 606463.0001) mutation in the GBA gene.

Koprivica et al. (2000) found that homozygosity for L444P was ...
Population genetics OMIM The Swedish families with the Norrbottnian type of Gaucher disease are found in 2 geographically distinct clusters. Dahl et al. (1990; 1993) demonstrated that both clusters are caused by the same GBA mutation (L444P). Mutation analysis was combined ...