Gaucher disease type 2

General Information (adopted from Orphanet):

Synonyms, Signs: GD II
Gaucher disease, acute neuronopathic type
Infantile cerebral Gaucher disease
Acute neuronopathic Gaucher disease
Number of Symptoms 167
OrphanetNr: 77260
OMIM Id: 230900
ICD-10: E75.2
UMLs: C0268250
MeSH:
MedDRA:
Snomed: 12246008

Prevalence, inheritance and age of onset:

Prevalence: < 0.1 of 100 000
Inheritance: Autosomal recessive
25755533 [IBIS]
Age of onset: Neonatal
Infancy
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 II is caused by homozygous or compound heterozygous mutation in the gene encoding acid beta-glucosidase (GBA) (OMIM). Type 2 Gaucher disease (GD) is a neuronopathic from of disease with severe neurological disease and is usually fatal by 2 years of age. The neurological involvement is a more severe involvement of that seen in GD3. (PMID:25755533)

Symptom Information: Sort by abundance 

1
 (HPO:0002795) Functional respiratory abnormality Rare [IBIS] 20880730 IBIS 13 / 7739
2
 (HPO:0000132) Menorrhagia 25755533 IBIS 40 / 7739
3
 (HPO:0001999) Abnormal facial shape Occasional [IBIS] 25435509; 20880730 IBIS 169 / 7739
4
 (HPO:0000253) Progressive microcephaly 20880730 IBIS 37 / 7739
5
 (HPO:0012472) Eclabion 26646163 IBIS 7 / 7739
6
 (HPO:0000421) Epistaxis 25755533 IBIS 85 / 7739
7
 (HPO:0000252) Microcephaly 21889374; 25435509 IBIS 832 / 7739
8
 (HPO:0000211) Trismus 25435509 IBIS 9 / 7739
9
 (HPO:0000656) Ectropion 26646163; 20880730 IBIS 25 / 7739
10
 (HPO:0001488) Bilateral ptosis 20880730 IBIS 42 / 7739
11
 (HPO:0007957) Corneal opacity 25755533 IBIS 84 / 7739
12
 (HPO:0000514) Slow saccadic eye movements 25755533 IBIS 21 / 7739
13
 (HPO:0000605) Supranuclear gaze palsy 25755533; 20880730 IBIS 16 / 7739
14
 (HPO:0000486) Strabismus Frequent [IBIS] Very frequent [Orphanet] 25755533; 24588457; 21889374; 25435509 IBIS 576 / 7739
15
 (HPO:0000657) Oculomotor apraxia Occasional [IBIS] 25755533; 20880730; 20880730 IBIS 54 / 7739
16
 (HPO:0007885) Slowed horizontal saccades 20880730 IBIS 2 / 7739
17
 (HPO:0000602) Ophthalmoplegia 23430923 IBIS 56 / 7739
18
 (HPO:0000496) Abnormality of eye movement Very frequent [Orphanet] 20880730 IBIS 79 / 7739
19
 (HPO:0001254) Lethargy 25330526 IBIS 104 / 7739
20
 (HPO:0002530) Axial dystonia 23430923 IBIS 6 / 7739
21
 (HPO:0002376) Developmental regression 21889374 IBIS 74 / 7739
22
 (HPO:0001263) Global developmental delay Frequent [IBIS] 25755533; 25330526; 23430923; 21889374 IBIS 853 / 7739
23
 (HPO:0001250) Seizures Frequent [Orphanet] 25755533; 26646163; 25330526; 25435509 IBIS 1245 / 7739
24
 (HPO:0002179) Opisthotonus Frequent [IBIS] 25755533; 25330526; 23430923; 21889374; 21889374; 25435509; 25435509 IBIS 35 / 7739
25
 (HPO:0001251) Ataxia 25755533 IBIS 413 / 7739
26
 (HPO:0012378) Fatigue 25755533 IBIS 50 / 7739
27
 (HPO:0011349) Abducens palsy 20880730 IBIS 7 / 7739
28
 (HPO:0001270) Motor delay 23430923 IBIS 322 / 7739
29
 (HPO:0002509) Limb hypertonia 23430923; 21889374 IBIS 13 / 7739
30
 (HPO:0002304) Akinesia 26327947 IBIS 18 / 7739
31
 (HPO:0002063) Rigidity 25755533; 25435509 IBIS 92 / 7739
32
 (HPO:0001276) Hypertonia Very frequent [Orphanet] 25755533; 26327947; 25435509 IBIS 317 / 7739
33
 (HPO:0002305) Athetosis 20880730 IBIS 31 / 7739
34
 (HPO:0002015) Dysphagia 23430923; 20880730 IBIS 301 / 7739
35
 (HPO:0000726) Dementia 25755533 IBIS 131 / 7739
36
 (HPO:0002344) Progressive neurologic deterioration 23430923; 21889374 IBIS 27 / 7739
37
 (HPO:0001336) Myoclonus 25755533; 25435509 IBIS 115 / 7739
38
 (HPO:0002375) Hypokinesia 25435509 IBIS 25 / 7739
39
 (HPO:0001257) Spasticity 24588457; 25435509 IBIS 251 / 7739
40
 (HPO:0011296) EEG with temporal sharp waves 26646163 IBIS 1 / 7739
41
 (HPO:0000737) Irritability 25435509 IBIS 93 / 7739
42
 (HPO:0011097) Epileptic spasms 20880730 IBIS 45 / 7739
43
 (HPO:0000817) Poor eye contact 21889374 IBIS 26 / 7739
44
 (HPO:0012229) CSF pleocytosis 25330526 IBIS 5 / 7739
45
 (HPO:0006380) Knee flexion contracture 26646163 IBIS 56 / 7739
46
 (HPO:0005146) Cardiac valve calcification 25755533 IBIS 4 / 7739
47
 (HPO:0002653) Bone pain 25755533 IBIS 75 / 7739
48
 (HPO:0002750) Delayed skeletal maturation 25755533 IBIS 250 / 7739
49
 (HPO:0002650) Scoliosis 25755533 IBIS 705 / 7739
50
 (HPO:0005743) Avascular necrosis of the capital femoral epiphysis 25755533 IBIS 17 / 7739
51
 (HPO:0004975) Erlenmeyer flask deformity of the femurs 25755533 IBIS 8 / 7739
52
 (HPO:0002808) Kyphosis 25755533 IBIS 289 / 7739
53
 (HPO:0000765) Abnormality of the thorax 25755533 IBIS 64 / 7739
54
 (HPO:0000938) Osteopenia 25755533 IBIS 138 / 7739
55
 (HPO:0005789) Generalized osteosclerosis 25755533 IBIS 10 / 7739
56
 (HPO:0002987) Elbow flexion contracture 26646163 IBIS 64 / 7739
57
 (HPO:0001371) Flexion contracture 26327947; 25435509 IBIS 220 / 7739
58
 (HPO:0002797) Osteolysis 25755533 IBIS 68 / 7739
59
 (HPO:0001217) Clubbing 25755533 IBIS 39 / 7739
60
 (HPO:0001789) Hydrops fetalis 26327947; 25435509; 20880730 IBIS 63 / 7739
61
 (HPO:0001558) Decreased fetal movement 26327947 IBIS 74 / 7739
62
 (HPO:0001561) Polyhydramnios 26327947 IBIS 191 / 7739
63
 (HPO:0001790) Nonimmune hydrops fetalis 24588457; 20880730 IBIS 15 / 7739
64
 (HPO:0001989) Fetal akinesia sequence 20880730 IBIS 14 / 7739
65
 (HPO:0001399) Hepatic failure 20880730 IBIS 80 / 7739
66
 (HPO:0002027) Abdominal pain 25755533 IBIS 184 / 7739
67
 (HPO:0001538) Protuberant abdomen 23430923; 21889374 IBIS 36 / 7739
68
 (HPO:0001433) Hepatosplenomegaly Very frequent [IBIS] 25755533; 24588457; 26842663; 26646163; 25330526, 23430923; 21889374; 25435509 IBIS 78 / 7739
69
 (HPO:0001396) Cholestasis 23430923; 25435509 IBIS 136 / 7739
70
 (HPO:0001409) Portal hypertension Rare [IBIS] 25755533; 25435509 IBIS 39 / 7739
71
 (HPO:0002013) Vomiting 25435509; 20880730 IBIS 191 / 7739
72
 (HPO:0001537) Umbilical hernia 23430923 IBIS 206 / 7739
73
 (HPO:0002039) Anorexia 20880730 IBIS 62 / 7739
74
 (HPO:0002033) Poor suck 25435509 IBIS 37 / 7739
75
 (HPO:0002584) Intestinal bleeding 20880730 IBIS 16 / 7739
76
 (HPO:0001081) Cholelithiasis 25755533 IBIS 36 / 7739
77
 (HPO:0001541) Ascites 26646163 IBIS 94 / 7739
78
 (HPO:0002018) Nausea 20880730 IBIS 44 / 7739
79
 (HPO:0002910) Elevated hepatic transaminases 26646163; 23430923; 25435509 IBIS 158 / 7739
80
 (HPO:0002020) Gastroesophageal reflux 26842663 IBIS 101 / 7739
81
 (HPO:0008872) Feeding difficulties in infancy 25330526; 25435509 IBIS 153 / 7739
82
 (HPO:0002240) Hepatomegaly Very frequent [Orphanet] 25755533; 26327947 IBIS 467 / 7739
83
 (HPO:0001394) Cirrhosis 25755533 IBIS 102 / 7739
84
 (HPO:0200084) Giant cell hepatitis 23430923 IBIS 8 / 7739
85
 (HPO:0000952) Jaundice 23430923; 20880730; 20880730 IBIS 105 / 7739
86
 (HPO:0001743) Abnormality of the spleen 25755533 IBIS 37 / 7739
87
 (HPO:0002014) Diarrhea 25755533 IBIS 225 / 7739
88
 (HPO:0001402) Hepatocellular carcinoma 25755533 IBIS 25 / 7739
89
 (HPO:0001744) Splenomegaly Very frequent [Orphanet] 25755533 IBIS 337 / 7739
90
 (HPO:0001508) Failure to thrive Frequent [IBIS] 23430923; 21889374; 25435509 IBIS 454 / 7739
91
 (HPO:0001511) Intrauterine growth retardation 26646163; 20880730 IBIS 358 / 7739
92
 (HPO:0004325) Decreased body weight Very frequent [Orphanet] 25435509 IBIS 492 / 7739
93
 (HPO:0001072) Thickened skin 26327947 IBIS 87 / 7739
94
 (HPO:0001933) Subcutaneous hemorrhage 20880730 IBIS 50 / 7739
95
 (HPO:0000967) Petechiae 25755533 IBIS 26 / 7739
96
 (HPO:0000961) Cyanosis 25755533 IBIS 60 / 7739
97
 (HPO:0007479) Congenital nonbullous ichthyosiform erythroderma 26646163; 25435509; 20880730 IBIS 13 / 7739
98
 (HPO:0007420) Spontaneous hematomas 25755533 IBIS 9 / 7739
99
 (HPO:0000979) Purpura 26646163; 20880730 IBIS 27 / 7739
100
 (HPO:0000980) Pallor 25330526 IBIS 52 / 7739
101
 (HPO:0000951) Abnormality of the skin 26327947 IBIS 147 / 7739
102
 (HPO:0007431) Congenital ichthyosiform erythroderma 24588457; 25435509; 20880730 IBIS 17 / 7739
103
 (HPO:0001635) Congestive heart failure 25755533 IBIS 232 / 7739
104
 (HPO:0011675) Arrhythmia 25755533; 20880730 IBIS 226 / 7739
105
 (HPO:0002092) Pulmonary hypertension 25755533; 20880730 IBIS 109 / 7739
106
 (HPO:0002170) Intracranial hemorrhage 25435509 IBIS 40 / 7739
107
 (HPO:0001279) Syncope 25755533 IBIS 94 / 7739
108
 (HPO:0100727) Histiocytosis 25330526 IBIS 2 / 7739
109
 (HPO:0001903) Anemia Frequent [IBIS] 25755533; 26646163; 23430923; 25435509 IBIS 289 / 7739
110
 (HPO:0012156) Hemophagocytosis 25330526 IBIS 9 / 7739
111
 (HPO:0001882) Leukopenia 25755533 IBIS 51 / 7739
112
 (HPO:0001928) Abnormality of coagulation 25330526 IBIS 44 / 7739
113
 (HPO:0006775) Multiple myeloma 25755533 IBIS 10 / 7739
114
 (HPO:0001873) Thrombocytopenia Frequent [IBIS] 25755533; 24588457; 26842663; 26646163, 23430923; 23430923; 25435509 IBIS 224 / 7739
115
 (HPO:0001876) Pancytopenia 25330526 IBIS 89 / 7739
116
 (HPO:0004377) Hematological neoplasm 25755533 IBIS 12 / 7739
117
 (HPO:0001892) Abnormal bleeding 25755533; 24588457; 25435509 IBIS 85 / 7739
118
 (HPO:0002917) Hypomagnesemia 25435509 IBIS 19 / 7739
119
 (HPO:0000969) Edema 25330526 IBIS 117 / 7739
120
 (HPO:0002901) Hypocalcemia 25435509 IBIS 56 / 7739
121
 (HPO:0003281) Increased serum ferritin 25330526 IBIS 32 / 7739
122
 (HPO:0001943) Hypoglycemia 25435509 IBIS 131 / 7739
123
 (HPO:0002902) Hyponatremia 25435509 IBIS 37 / 7739
124
 (HPO:0001987) Hyperammonemia 25435509 IBIS 50 / 7739
125
 (HPO:0002904) Hyperbilirubinemia 26646163 IBIS 32 / 7739
126
 (HPO:0001945) Fever 25330526; 20880730 IBIS 218 / 7739
127
 (HPO:0003656) Decreased beta-glucocerebrosidase protein and activity Very frequent [IBIS] 25755533; 25330526; 23430923; 26327947 IBIS 5 / 7739
128
 (HPO:0011951) Aspiration pneumonia 20880730 IBIS 6 / 7739
129
 (HPO:0006530) Interstitial pulmonary disease 25435509 IBIS 26 / 7739
130
 (HPO:0002793) Abnormal pattern of respiration Very frequent [Orphanet] 25755533 IBIS 26 / 7739
131
 (HPO:0006511) Laryngeal stridor 20880730 IBIS 6 / 7739
132
 (HPO:0012418) Hypoxemia 25435509 IBIS 18 / 7739
133
 (HPO:0002089) Pulmonary hypoplasia 20880730 IBIS 80 / 7739
134
 (HPO:0002094) Dyspnea 25755533 IBIS 132 / 7739
135
 (HPO:0002205) Recurrent respiratory infections Frequent [Orphanet] 25755533 IBIS 254 / 7739
136
 (HPO:0002835) Aspiration 20880730 IBIS 11 / 7739
137
 (HPO:0002875) Exertional dyspnea 25755533 IBIS 29 / 7739
138
 (HPO:0002104) Apnea 23430923; 25435509; 25435509 IBIS 106 / 7739
139
 (HPO:0002098) Respiratory distress 26646163; 25435509 IBIS 75 / 7739
140
 (HPO:0001600) Abnormality of the larynx 25435509 IBIS 15 / 7739
141
 (HPO:0002716) Lymphadenopathy 25755533 IBIS 129 / 7739
142
 (HPO:0001283) Bulbar palsy 25755533 IBIS 31 / 7739
143
 (HPO:0001290) Generalized hypotonia 21889374 IBIS 51 / 7739
144
 (MedDRA:10026820) Marasmus 23430923 IBIS 1 / 7739
145
 (MedDRA:10052274) Hepatopulmonary syndrome 25755533 IBIS 3 / 7739
146
 (HPO:0002483) Bulbar signs 23430923; 25435509 IBIS 9 / 7739
147
 (MedDRA:10008589) Choking 25435509 IBIS 6 / 7739
148
 (HPO:0003826) Stillbirth 20880730 IBIS 40 / 7739
149
 (HPO:0030402) Abnormal platelet aggregation 25435509 IBIS 1 / 7739
150
 (HPO:0012444) Brain atrophy 21889374 IBIS 24 / 7739
151
 (MedDRA:10063473) Chitotriosidase increased 26327947 IBIS 1 / 7739
152
 (OMIM) Pitting edema 25330526 IBIS 3 / 7739
153
 (OMIM) Hemophagocytic lymphohistiocytosis 25330526 IBIS 3 / 7739
154
 (OMIM) Retroflexion of the neck 23430923 IBIS 1 / 7739
155
 (OMIM) Bone crises 25755533 IBIS 3 / 7739
156
 (MedDRA:10035060) Pinguecula 25755533 IBIS 4 / 7739
157
 (MedDRA:10023891) Laryngospasm 25435509 IBIS 4 / 7739
158
 (HPO:0001522) Death in infancy Very frequent [IBIS] Very frequent [Orphanet] 25755533; 21889374; 25435509 IBIS 275 / 7739
159
 (OMIM) Laryngeal spasms 25435509 IBIS 1 / 7739
160
 (MedDRA:10041648) Splenic infarction 25755533 IBIS 3 / 7739
161
 (HPO:0012764) Orthopnea 25755533 IBIS 9 / 7739
162
 (HPO:0030148) Heart murmur 21889374 IBIS 29 / 7739
163
 (MedDRA:10057870) Head lag 21889374 IBIS 3 / 7739
164
 (OMIM) Absent gag reflex 20880730 IBIS 4 / 7739
165
 (MedDRA:10058679) Skin oedema 26327947 IBIS 1 / 7739
166
 (MedDRA:10059186) Early satiety 25755533 IBIS 4 / 7739
167
 (HPO:0007366) Atrophy/Degeneration affecting the brainstem 20880730 IBIS 4 / 7739

Associated genes:

GBA;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
GBA rs1064651 pathogenic RCV000004524.5
GBA rs1135675 pathogenic RCV000004534.4
GBA rs121908295 pathogenic RCV000004514.4
GBA rs121908305 pathogenic RCV000004562.2
GBA rs121908306 pathogenic RCV000004563.2
GBA rs367968666 pathogenic RCV000004580.2
GBA rs381737 pathogenic RCV000004541.4
GBA rs421016 pathogenic RCV000004509.8
GBA rs76539814 pathogenic RCV000041967.6
GBA rs80356759 pathogenic RCV000004546.4
GBA rs80356771 pathogenic RCV000004529.4

Additional Information:

Description: (OMIM) Type II Gaucher disease is an acute neuronopathic form of the disorder with onset in infancy and death often by 2 years of age. Patients are usually normal at birth, but develop hepatosplenomegaly, developmental regression, and growth arrest ...
Clinical Description OMIM Owada et al. (1977) reported 3 Japanese patients with neuronopathic Gaucher disease. Glucocerebrosidase activity was almost normal in the liver, but markedly reduced in the spleen and fibroblasts.

Saranjam et al. (2013) reported 2 unrelated infants ...
Molecular genetics OMIM Tsuji et al. (1987) identified a homozygous mutation in the GBA gene (L444P; 606463.0001) in patients with Gaucher disease type II.

Wigderson et al. (1989) reported a patient with type II disease who was compound heterozygous ...