What is Gaucher disease Type 1?

Gaucher disease Type 1 is the most common form of the disease and is distinguished from Gaucher disease Type 2 and Gaucher disease Type 3 in that it does not have a neurological component. The clinical presentation of Gaucher disease Type 1 is variable; patients may present early in childhood, during adulthood, or may be asymptomatic throughout their life.1 The observed clinical presentations of Gaucher disease Type 1 are outlined below and in Figure 1.

Visceral and haematological disease

Splenomegaly (enlarged spleen)2 and hepatomegaly (enlarged liver)3 are observed in 90% and 60‒80% of patients with Gaucher disease Type 1, respectively.1 This enlargement is a result of the accumulation of Gaucher cells in the spleen and liver, and can lead to abdominal distension.1,4 Data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry (sponsored by Sanofi Genzyme), published in 2015, indicated that approximately 30% of patients with Gaucher disease Type 1 had splenic volumes ≥15 MN (multiples of normal based on 0.2% of body weight) and approximately 55% of patients had spleen sizes 5‒15 MN. Similarly, 53% of patients with Gaucher disease Type 1 had hepatomegaly 1.25‒2.5 MN (multiples of normal based on 2.5% of body weight).5 Along with hypersplenism (rapid and premature destruction of blood cells by the spleen),6 accumulating Gaucher cells in the bone marrow can lead to pancytopaenia, which is defined as an abnormally low level of red and white blood cells, as well as platelets, in the circulating blood.4,7,8 In patients with intact spleens, hepatomegaly is almost always present but is often not massive unless splenomegaly is also present.4 If a patient with Gaucher disease has a disproportionately enlarged liver compared with the degree of splenomegaly, then other causes of hepatomegaly should be considered.7 Moreover, up to 40% of patients may also have focal splenic and/or hepatic lesions, which are associated with severe disease.9

Patients with Gaucher disease Type 1 may present with thrombocytopaenia, which is an abnormal reduction in the number of platelets.7,10 For example, in childhood, this may present as epistaxis, easy bruising or overt bleeding. Thrombocytopaenia may also be associated with trauma, surgery or pregnancy.4 Clinically significant thrombocytopaenia may occur even if haemoglobin levels are within normal ranges.7 Among the patients with Gaucher disease Type 1 enrolled in the ICGG Gaucher Registry, 15% had severe thrombocytopaenia (≤60,000/mm3), whereas less severe thrombocytopaenia (≤60,000 to 120,000/mm3) was evident in 50‒70% of patients.5

Fatigue and anaemia are additional symptoms of Gaucher disease Type 1.1 Approximately 20‒30% of patients with Gaucher disease Type 1 from the ICGG Gaucher Registry presented with anaemia at diagnosis.5 However, it should be noted that if a patient with Gaucher disease Type 1 (not splenectomised) presents with significant anaemia but normal or near-normal platelet counts, other causes of anaemia should be considered. An aetiology of anaemia itself may not be related to Gaucher disease and instead may be due to nutritional causes or secondary bleeding.7 Acquired coagulation, deficient neutrophil function, excess ferritin, gallstones and vitamin B12 deficiency have also been reported in patients with Gaucher disease Type 1.4,11

In patients with Gaucher disease Type 1, leukopaenia, an abnormally low level of leukocytes in the circulating blood,12 is rare but may be due to hypersplenism. However, leukopaenia is rarely so severe that it requires intervention.1,7

Acute painful bone crises may present as a sudden onset of excruciating pain associated with swelling and erythema, fever and leukocytosis in patients with Gaucher disease Type 1.1,13 Afterwards, the bone is often severely damaged and a fracture may occur followed by secondary degenerative osteoarthritis.4

Avascular necrosis (or osteonecrosis) is believed to be secondary to ischaemia from chronic infarction. This condition leads to bone death, which is irreversible and can cause fracture and joint collapse in patients with Gaucher disease.13

Osteopaenia (reduced bone mass)14 and osteoporosis (loss of protein and mineral content causing porous bones)15 occur earlier in the disease, are more severe in patients with Gaucher disease Type 1, and may lead to pathological fractures.1 Infiltration of Gaucher cells into the bone marrow can lead to fibrosis and impaired haematopoiesis. Bioactive lipids that originate from Gaucher cells may engage other bone marrow cell types (e.g. osteoblasts and endothelial cells), and may culminate in avascular necrosis and osteopaenia.16

Patients with Gaucher disease may also experience a condition described as Erlenmeyer flask deformity; however, this is not necessarily a symptom and is not specific to Gaucher disease. This deformity is caused by an impairment of remodelling of the metaphyseal and tubular bones, and manifests as flaring of the distal lateral aspects of the femur and proximal tibia.17

Many patients with Gaucher disease Type 1 enrolled in the ICGG Gaucher Registry had symptomatic or radiological imaging evidence of bone disease at Gaucher disease onset. Approximately 40% of patients had Erlenmeyer flask deformity, approximately 20% had osteopaenia, approximately 10% had bone crises, and evidence of avascular necrosis in any bone or evidence of infarction was detected in approximately 10‒20% of patients.5

Modelling and remodelling abnormalities of bones in patients with Gaucher disease can also result in developmental changes, cortical thinning, lytic lesions and fragility fractures.18 Children may experience delays in growth and puberty (growth <5th percentile).19

Clinical evidence from studies of patients with Gaucher disease Type 1:

  • Low appetite was reported in 24.2% of patients with Gaucher disease Type 1.20
  • In one Spanish study, 2‒9% of adults were reported to be underweight and 20‒46% were overweight (6‒8% were obese).21
  • Basal hepatic glucose was elevated by 30% in treatment-naïve patients with Gaucher disease Type 1 compared with healthy individuals.22
  • Cumulative incidence of Type 2 diabetes has been reported as 6.6% in patients with Gaucher disease Type 1.23
  • Changes in lipoprotein concentrations are apparent in patients with Gaucher disease Type 1; serum concentrations of total cholesterol, and low-density lipoprotein and high-density lipoprotein cholesterol, are often low in untreated patients.24,25

Despite Gaucher disease Type 1 being the non-neuronopathic form of the disease, when compared with the general population, there is an increased incidence of peripheral neuropathy in patients (0.0046‒0.015 per 100 person-years vs 2.9 per 100 person-years).26-28 Patients with Gaucher disease Type 1 are also at a higher risk of developing Parkinson’s disease (20-fold increased lifetime risk compared with the general population).29,30

  • It has been reported that patients with Gaucher disease Type 1 have an increased risk of certain haematological malignancies (multiple myeloma and non-myeloma).4
  • Although rare, infiltration of the lungs by Gaucher cells may lead to pulmonary involvement, and may culminate in pulmonary fibrosis, restrictive lung disease secondary to spinal deformation, or pulmonary arterial hypertension.31
  • Proteinuria and haematuria reflect infiltration of Gaucher cells into glomeruli; however, renal involvement is rare.32
  • Yellow-brown hyperpigmentation and ‘easy tanning’ can occur as a result of skin involvement.33
  • Ocular manifestations can occur but are rarely observed.34-36
  • Myocardial or valvular involvement have been reported but are rare.37

Figure 1.
Clinical features of Gaucher disease Type 1

Clinical features of patients with Gaucher disease Type 1: descriptive analysis from the Gaucher Outcome Survey (GOS) 2017

The GOS is an international Gaucher disease registry (sponsored by Shire, now part of Takeda) that was first established in 2010 for patients who had a confirmed diagnosis of Gaucher disease, regardless of disease type and treatment status. By 25 February 2017, 1209 patients had enrolled, the majority of whom were from Israel (44.3%) and the US (31.4%). Most patients had Gaucher disease Type 1 (91.5%), and 13.3% had undergone a total splenectomy. The median age (interquartile range) of Gaucher disease diagnosis was 40.4 (26.5‒56.8) years, and 44.1% were male.38


Haematological and visceral findings at the time of entry into the GOS were close to normal for most patients; this finding was possibly a result of treatment38:

  • 73.5% had a normal haemoglobin concentration (defined as ≥11.0 g/dL for women and children, and ≥12.0 g/dL for men).
  • 58.9% had platelet counts ≥120 x 109/L, and 18.6% and 4.0% of patients had a platelet count of ≥60‒120 x 109/L and <60 x 109/L, respectively.


For patients in Israel, spleen volume was almost double that of patients from other countries (7.2 multiple of normal [MN] vs 2.7 MN, 2.9 MN and 4.9 MN found in the US, UK and rest of the world, respectively).38


Liver volume was slightly higher in patients from Israel (1.1 MN) compared with those from the US (1.0 MN), UK (0.8 MN) and rest of the world (0.8 MN).38

At GOS entry, 34.2% (n=413/1209) of patients had ≥1 skeletal abnormality, as observed by orthopaedic imaging38:

  • 21.5% bone marrow infiltration
  • 15.1% Erlenmeyer flask deformities
  • 11.8% avascular necrosis
  • 3.7% fractures.

Of the 350 patients with available data, 111 (31.7%) patients reported bone pain; this finding was classified as severe for 20 (5.7%) patients by the treating physician.38


Clinical features of paediatric patients with Gaucher disease Type 1: a longitudinal observational study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry 2005

This was a longitudinal observational study to describe the clinical and demographic characteristics of Gaucher disease Type 1 in paediatric patients (aged <18 years). Data reported from 1 January 1989 to 3 June 2005 were included in the study. Of the 887 patients (51% male) included, 29% were from the US, 25% from Latin America, 19% from Europe and 15% from Israel. Most patients (48%) were diagnosed at age 0 to <6 years. The remaining patients were diagnosed at age 6 to <12 years (31%) or at age 12 to <18 years (21%).1


Across all age groups, haematological and organ volume disease manifestations were reported as follows19:

  • 71% moderate hepatomegaly (liver volume >1.25‒2.5 MN; n=168/237)
  • 16% severe hepatomegaly (liver volume >2.5 MN; n=37/237)
  • 44% moderate splenomegaly (spleen volume >5‒15 MN; n=106/241)
  • 51% severe splenomegaly (spleen volume >15 MN; n=124/241)
  • 41% moderate thrombocytopaenia with spleen intact (platelet count 60 to <120 x 103/µL; n=231/570)
  • 9% severe thrombocytopaenia (platelet count <60 x 103/µL; n=51/570)
  • 40% anaemia* (n=239/602).


Younger (aged 0 to <6 years or 6 to <12 years) patients tended to have significantly more abnormalities in haemoglobin levels (p<0.05), and spleen and liver volumes (p<0.001), than older (aged 12 to <18 years) paediatric patients. The proportion of patients aged 12 to <18 years with severe or moderate thrombocytopaenia with intact spleen was higher than younger (aged 0 to <6 years or 6 to <12 years) patients (p=0.003).19


The prevalence of skeletal manifestations across all age groups was reported as19:

  • 81% any evidence of radiological bone disease (n=246/304)
    • 49% Erlenmeyer flask deformity (n=150/304)
    • 38% marrow infiltration (n=116/304)
    • 20% osteopaenia (n=62/304)
    • 8% infarction (n=24/304)
    • 8% avascular necrosis (n=23/304)
    • 7% lytic lesions (n=21/304)
    • 2% new fractures (n=6/304)
  • 34% growth retardation (height <5th percentile; n=167/496)
  • 27% bone pain (n=124/460)
  • 9% bone crises (n=39/449).


Older (aged 12 to <18 years) children had significantly more severe skeletal disease than younger (aged 0 to <6 years or 6 to <12 years) patients (p<0.001).19

*Anaemia is defined according to age and sex norms for haemoglobin concentrations as follows: <11 g/dL for boys aged ≥12 years; <10 g/dL for girls aged ≥12 years; <9.5 g/dL for children aged ≥2 years to <12 years; <8.5 g/dL for children aged ≥6 months to <2 years; and <9.1 g/dL for infants aged ≤6 months19


C-ANPROM/INT//7566; Date of preparation: September 2020