About Gaucher Disease

Gaucher Disease is the most common lipid storage disorder and is the most common genetic disease affecting Jewish people of Eastern European ancestry. Gaucher Disease results from a specific enzyme deficiency, caused by an autosomal recessive genetic mutation. The disease course is quite variable, ranging from no outward symptoms to severe disability and death.

Gaucher disease is characterized by decreased levels of the enzyme glucocerebrosidase. This deficiency of glucocerebrosidase leads to the accumulation of the lipid glucocerebroside within the lysosomes of the monocyte/macrophage system.

Lipid-engorged cells with eccentric nuclei (known as Gaucher cells) displace healthy, normal cells in the body - typically in the liver, spleen and bone marrow - which can lead to hepatosplenomegaly, organ dysfunction, and skeletal deterioration.

Gaucher Disease is generally described by clinical presentation:

• Type 1 nonneuronopathic is the most common, with onset of symptoms at any age in childhood through adulthood. This type is panethnic, but more prevalent in people of Eastern European Jewish ancestry.
• Type 2 acute neuronopathic is characterized by central nervous system involvement. Onset of symptoms is in the first year of life and patients rarely survive beyond age two.
• Type 3 subacute neuronopathic is characterized by a variable course of central nervous system involvement that progresses and the systemic involvement seen in Type 1. Onset of symptoms is in childhood. A distinct cluster of Type 3 disease has been described in the area of Norrbotten, Sweden.

Symptomatology

Gaucher disease is extremely heterogeneous. Although over 200 mutations in the glucocerebrosidase gene have been identified, there are patients with the same mutation who exhibit very different clinical courses.

Type 1 Gaucher disease presents with one or more of the following:

• Skeletal complications: Gaucher patients can experience bone pain, bone lesions, osteopenia, osteonecrosis, avascular necrosis and pathological fractures. Skeletal involvement can be debilitating but is often unrecognized as a manifestation of Gaucher disease.
• Anemia: Gaucher patients can experience fatigue and general weakness due to decreased hemoglobin.
• Hepatosplenomagaly: Gaucher patients may have splenomegaly with hypersplenism and splenic infarcts. The liver is often enlarged but generally hepatocytes are spared.
• Thrombocytopenia:Gaucher patients can experience easy bruising and bleeding as a result of low platelet count.
• Delayed growth and pubertal development: These are common in children with Gaucher disease.

Diagnosis

Initial diagnosis of Gaucher disease may be difficult due to wide variability in symtomatology. Signs and symptoms shared with more common diseases such as leukemia, lymphoma or rheumatoid arthritis may delay diagnosis.

Spleen, liver, or bone marrow biopsies are sometimes performed and point towards a possible Gaucher disease diagnosis. This must be confirmed with an enzyme assay.

Enzyme analysis of leukocytes or fibroblast cultures will confirm or exclude the diagnosis of Gaucher disease.