Gaucher Disease

Key Points:


Gaucher disease is the most common inherited lysosomal storage disease, linked to a deficiency of glucocerebrosidase.


Gaucher disease is caused by a genetic defect in the enzyme β-glucocerebrosidase.  It has an autosomal recessive inheritance pattern and a prevalence of 1 in 40,000 in the general population and 1 in 400 to 1 in 600 among Ashkenazi Jews. Three forms of Gaucher disease are recognized: type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic). Type 1 is by far the most common form, is seen most frequently in the Ashkenazi population, and is characterized by hepatosplenomegaly, pancytopenia, and pre-dominant skeletal manifestations. Type 2 is a rare form that involves the central nervous system and cranial nerves and usually causes death by apnea or aspiration before the age of 2 years. Type 3 is characterized by neurologic symptoms, including seizures that begin during adolescence. 

Clinical Findings:

A patient with Gaucher disease can have asymptomatic bone lesions, or may present with pain, deformity, osteopenia, osteonecrosis, osteomyelitis, pathologic fracture, and vertebral collapse. Bone pain, fracture and growth retardation are the most common musculoskeletal presenting symptoms. Skeletal abnormalities are detected radiographically in 80-90% of patients at presentation. Other clinical manifestations depend on which organs are affected by accumulated Gaucher cells. Splenic involvement causes splenomegaly and can lead to anemia, thrombocytopenia, or pancytopenia. Liver involvement can cause impaired hepatic synthesis of clotting factors, causing coagulopathy.  

Bone crises are a common symptom of skeletal involvement, which are thought to be related to intramedullary or subperiosteal hemorrhage made possible by thrombocytopenia and deficient clotting factor synthesis. Symptoms can include fever, leukocytosis, and elevated erythrocyte sedimentation rate, meaning that bone crises often mimic osteomyelitis, so blood cultures may help differentiate between the two. 

Osteonecrosis can follow a bone crisis, and occurs in 12% to 34% of patients with Gaucher disease. Common sites include the femoral head, femoral condyle, tibial plateau, and humeral head. 

Osteopenia can also result in vertebral compression fracture and acute kyphotic deformities, such as a gibbus

Imaging Studies:

Gaucher disease can be associated with a classic “Erlenmeyer flask” deformity of the distal femur and proximal tibia on radiographs.  This represents impairment of remodeling. This finding, however, is not pathognomonic for Gaucher disease and occurs only in 56% to 70% of affected patients.  

Spine X-Rays of Gaucher patients may show endplate changes that have been described as “step-off, H-type, or fish mouth.”  This represents collapse of the vertebral body and subsequent growth recovery peripherally. 

Early in bone crises, plain radiographs are normal, but may progress to show periosteal reaction and areas of radiolucency. Radionuclide bone scans may show an area of decreased uptake early in the course of the process and increased uptake around an osteopenic area later in the course. MRI shows marrow edema on T2-weighted images, with or without signs of hemorrhage. Periosteal fluid accumulation seen on MRI may indicate infection or hemorrhage and, if lab studies are concerning for infection, can be aspirated for culture under sterile conditions and radiographic guidance.  Osteomyelitis rates for Gaucher’s disease were higher when aspiration was performed routinely for fluid collections without having confirmatory lab results first.


Treatment of bone crises is supportive. Severe pain early in the course usually requires opioid analgesics, which can be augmented with high-dose steroids. The symptoms gradually abate over 2 to 4 weeks.  

Failure of the symptoms to improve should warrant further investigation into the possibility of osteomyelitis.
Osteomyelitis can follow a bone crisis, often with anaerobic organisms, suggesting that there has been a period of ischemia.  

Back pain is common in children with spinal involvement, and may be severe enough to require bracing. Gibbus or acute kyphotic deformity can occur due to vertebral osteopenia and collapse of the anterior column. If cord compression or neurological signs are present, posterior instrumentation with or without anterior decompression may be required. 

Because Gaucher disease is a deficiency of a specific enzyme, enzyme replacement therapy (ERT) is the cornerstone of treatment. Replacement of macrophage-directed glucocerebrosidase has become standard medical treatment for type 1 Gaucher disease. Given intravenously at 2-week intervals, ERT reliably reverses anemia, thrombocytopenia, and splenomegaly. Enzyme replacement, if started early in life, can prevent skeletal deformity and allow normal skeletal development and growth, as well as decrease the incidence of  bone crises and fractures. ERT has been more effective in improving hematologic factors and organomegaly, but less effective at reversing bone lesions.


Fracture healing is impaired in patients with untreated Gaucher disease, so delayed union and nonunion are common. Osteopenia is nearly universal in Gaucher disease in children. Osteopenia can affect both trabecular and cortical bone. It can present as a focal or diffuse process. Pathologic fractures are not uncommon in patients with Gaucher disease, occurring in 23% of patients. The common sites of fracture are the distal femur, proximal tibia, and femoral neck.  

Fractures at the base of the femoral neck occur in young children and can be complicated by coxa vara, pseudoarthrosis, and osteonecrosis. Vertebral compression fractures occur with spinal involvement and can lead to severe kyphosis and spinal cord compromise on rare occasions. 

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Chris Hardesty, MD