Signs and Symptoms

Type 1 Gaucher disease is a heterogeneous disorder that may present with one or more of a wide array of signs and symptoms throughout the body. At first clinical presentation, some degree of visceromegaly and some skeletal pathology is usually present, although this may not be readily apparent at general physical examination. The skeletal pathologies usually are painful and debilitating. No symptom or sign (other than deficient glucocerebrosidase activity) is obligatory at any stage of Gaucher disease.

Signs and symptoms may be classified by the involved anatomical compartments. The most frequently involved are visceral, hematologic, skeletal, and metabolic. Physicians may find these groupings useful in narrowing the diagnostic investigation and ordering appropriate tests. The Diagnosing Gaucher section of this website provides an overview.

Signs and symptoms of Gaucher disease may also appear common to other conditions and physicians may not always immediately consider Gaucher disease in the differential diagnosis.[1] Recognizing a cluster of symptoms can often facilitate an earlier diagnosis of metabolic disorders such as Gaucher disease.

Click on one of the signs or symptoms below to find out more about Gaucher Disease.

Hepatosplenomegaly
Thrombocytopenia

Anemia

Leukopenia

Bone crisis

Osteonecrosis / avascular necrosis

Osteopenia

Pathological fracture

Erlenmeyer flask deformity

Hepatosplenomegaly

Gaucher disease patients may have protruding abdomens, from an enlarged liver and/or spleen, due to accumulation of Gaucher cells. The spleen can swell to greater than 15 times its normal size, while the liver can swell to 2.5 times its normal size. The involvement of these organs can have many other effects on patients, including suppressing the appetite (because the swelled organs press on the stomach, creating a full feeling after eating very little), blood problems related to an overactive spleen, complications of liver and splenic involvement, and low self-esteem related to appearance.

Enlarged spleen and liver in a child
Enlarged spleen and liver in a child

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, even after minor trauma. There may also be abnormalities in clotting and fibrinolytic factors.[1]

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. As a result, Gaucher patients may suffer from anemia. The resulting fatigue may also be exacerbated by a higher-than-normal metabolism found in many Gaucher patients.

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 get infections more frequently.

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. Management of a Gaucher bone crisis may require hospitalization.

Osteonecrosis / avascular necrosis

As Gaucher cells accumulate in bone marrow, they can restrict normal blood flow and thus restrict delivery of oxygen and nutrients to the bone -- sometimes leading to bone infarction and ultimately bone death. This causes severe pain and potentially leads to weakened bones, and to fractures and joint collapse.

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 thinning and weakening and thus greater susceptibility to fractures.

Pathological fracture

Weakened bones due to osteonecrosis, avascular necrosis and osteopenia are susceptible to pathological fractures from normal activity.

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.



Erlenmeyer flask of distal femur

References:

1. Beutler E, Grabowski GA. Gaucher disease. In: Scriver C, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001:3635-3668.

Lysosomal Storage Disorders

Gaucher disease is one of more than 40 rare inherited genetic disorders classified as a lysosomal storage disorder (LSD). Individually each LSD is relatively rare, but grouped together they affect about 1 in every 7,700 babies born. Learn more about Lysosomal Storage Disorders »

Gaucher Registry

For more than a decade, the Gaucher Registry has been a global resource to the medical and patient communities, helping to improve outcomes in patients with Gaucher disease. Learn more about participating in the Gaucher Registry »