Gaucher Disease

Gaucher disease is an inherited lysosomal storage disorder in which a deficiency of the enzyme glucocerebrosidase leads to the accumulation of the lipid glucocerebroside within the lysosomes of the monocyte-macrophage system.¹

Gaucher cells

Lipid-engorged cells with eccentric nuclei, known as Gaucher cells, accumulate and displace healthy normal cells in bone marrow and visceral organs, causing a range of manifestations, including skeletal deterioration, anemia, hepatosplenomegaly, and thrombocytopenia. In rare cases Gaucher cells affect the brain and nervous system.²

Gaucher disease is a panethnic disorder. It has been divided into three types based on the presence and severity of neurological involvement:

Type 1 (non-neuronopathic)

The most common type, it afflicts both children and adults. Incidence is 1 in 45,000-60,000 in the general population and 1 in 850 among people of Ashkenazi Jewish ancestry, with a carrier rate of 1 in 15 Ashkenazi Jews.³

Cerezyme is only indicated for treatment of Type 1 Gaucher disease. It is not indicated for treatment of Type 2 or Type 3 Gaucher disease.

Type 2 (acute neuronopathic) and Type 3 (chronic neuronopathic)

These less common forms of the disease are characterized by central nervous system involvement. Type 2 patients rarely survive to age 2. Type 3 is characterized by a variable course and is marked by slowly progressive neurological involvement. Prevalence of each type is <1 in 100,000.^4,5,6

Cerezyme is only indicated for treatment of Type 1 Gaucher disease. It is not indicated for treatment of Type 2 or Type 3 Gaucher disease.

Inheritance

Gaucher disease is an autosomal recessive disorder defined by the presence of two mutant alleles for the glucocerebrosidase gene.

With each pregnancy, each carrier of the mutated gene has a 50% chance of passing it on. When both parents are carriers, there is a 25% chance with each pregnancy that the child will develop Gaucher disease.

The diagrams below show how the Gaucher gene can be passed from one generation to the next.

Genetic counseling and testing

People at risk of being carriers may want to consider genetic counseling and family DNA testing. Individuals at risk include: relatives of Gaucher disease patients, people of Ashkenazi Jewish descent, and those with symptoms. 

Signs and Symptoms

Type 1 Gaucher disease is heterogeneous, presenting with a wide array of signs and symptoms throughout the body and progressing at variable rates. Signs and symptoms may be classified by four key anatomical compartments: visceral, hematologic, skeletal, and metabolic. These groupings may be useful in narrowing the diagnostic investigation and ordering appropriate tests.

Cerezyme is indicated for pediatric and adult patients with a confirmed diagnosis of Type 1 Gaucher disease that results in one or more of the following conditions: anemia, thrombocytopenia, bone disease, hepatomegaly or splenomegaly. These signs and symptoms are described below.

The skeletal pathologies associated with bone marrow infiltration can be particularly painful and debilitating, and are common. Up to 83% of patients have clinical or radiologic evidence of bone pain,⁷ and 34% are experiencing bone disease at the time of diagnosis.⁷ Among children, 72% are diagnosed with bone disease by age 6, and 92% are diagnosed with bone disease at ages 12 to 18.⁸

Since these signs and symptoms also appear with many other conditions, they may not be immediately recognized as Gaucher disease⁶, often creating an interval between symptom onset and diagnosis.⁹ To learn more, visit Diagnosing Gaucher disease.

Below are some specific signs and symptoms of Gaucher Disease⁶:

1. Hepatosplenomegaly

Gaucher patients may have protruding abdomens from enlarged liver and/or spleen, due to accumulation of Gaucher cells. The spleen can swell to 5-75 times its normal size, and the liver can swell to 1.25-2.5 times. The involvement of these organs can have other effects on patients, including appetite suppression (because the swelled organs press on the stomach, creating a full feeling), cytopenias related to an overactive spleen.

2. Thrombocytopenia

A build-up of Gaucher cells in bone marrow may cause fewer blood platelets to be produced. In addition, an enlarged, overactive spleen (caused by accumulated Gaucher cells) may break down blood cells faster than they are produced, contributing to an overall lower platelet count. As a result, Gaucher patients may experience excessive bruising and bleeding, including after minor trauma due to abnormalities in clotting and fibrinolytic factors.

3. Anemia

When the spleen is enlarged from accumulated Gaucher cells, it may become overactive and break down red blood cells faster than they are produced, contributing to anemia. The resulting fatigue may be exacerbated by the low stamina caused by a higher-than-normal metabolism found in many Gaucher patients.

4. Leukopenia

When the spleen is enlarged from accumulated Gaucher cells, it may become overactive and filter white blood cells faster than usual. As a result, Gaucher patients may be susceptible to infection.

5. Bone crisis

Gaucher patients may experience severe bone pain, or “bone crisis,” as a result of bone infarction (with insufficient blood flow and delivery of oxygen and nutrients to the bone) due to infiltration of Gaucher cells in the intramedullary space and local release of chemical factors. The pain is intense, often accompanied by fever, and can last from a few hours to a few days or even weeks, usually rendering patients bedridden during this time.

6. Osteopenia

Adult patients with Gaucher disease may have lower bone mass than expected for age and sex due to generalized demineralization, loss of trabecular bone and cortical thinning. This reduced bone density causes weakening and thus greater susceptibility to fractures.

7. Pathological fracture

Weakened bones due to osteopenia are susceptible to pathological fractures from normal activity.

8. Erlenmeyer flask deformity

Gaucher disease includes osteoclastic dysfunction and bone remodeling abnormalities. The most common among Gaucher patients is the Erlenmeyer flask deformity, in which the ends of the bone (most commonly the femur and tibia) develop a flared, flattened shape rather than the normal rounded form.

Indication & Usage

Cerezyme^® (imiglucerase for injection) is indicated for long-term enzyme replacement therapy for pediatric and adult patients with a confirmed diagnosis of Type 1 Gaucher disease that results in one or more of the following conditions:

1. anemia
2. thrombocytopenia
3. bone disease
4. hepatomegaly or splenomegaly

Important Safety Information

Approximately 15% of patients have developed IgG antibodies, and these patients have a higher risk of hypersensitivity reaction. Therefore periodic monitoring is suggested; caution should be exercised in patients with antibodies or prior symptoms of hypersensitivity. Symptoms suggestive of hypersensitivity occurred in 6.6% of patients, and include anaphylactoid reaction, pruritus, flushing, urticaria, angioedema, chest discomfort, dyspnea, coughing, cyanosis and hypotension.

Reactions related to Cerezyme administration have been reported in less than 15% of patients. Each of the following events occurred in less than 2% of the total patient population. Reported adverse events include nausea, abdominal pain, vomiting, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and tachycardia. Adverse events associated with the route of administration include discomfort, pruritus, burning, swelling or sterile abscess at the site at the site of injection.

To report suspected adverse reactions, contact Genzyme at 800-745-4447, option 2 or FDA at 800-FDA-1088 or http://www.fda.gov/Safety/MedWatch

Please see Full Prescribing Information (PDF).