Gaucher's Disease

- Discussion:
     - in 1882, Gaucher described idiopathic hypertrophy of spleen w/o leukemia;
     - results from autosomal recessive deficiency of lysosomal enzyme glucocerebrosidase (b-glucosidase), which ordinarily destoys the lipid material;
     - it is the most common genetic lysosomal storage disorder;
     - results in accumulation of of glucocerebroside in retinuloendothelia cells;
     - bone involvement is common in Gaucher's disease;
     - expansion and erosion of the cortices of bone with instances of AVN, bone crisis, and pathologic frx;
     - classification:
            - type I: (adult form)
                    - chronic noneuronopathic type;
                    - central nervous system is spared & disease is characterized by slowly progressive visceral and osseous involvement;
                    - enlarged spleen may cause mechanical problems, including abdominal distention and abdominal pain as well as
                            shortness of breadth, as well as causing pan cytopenia;
                            - splenectomy may be performed for thrombocytopenia;
                    - bone pain is a common complaint, which often resolves after 1-2 days;
                            - bone pain may also be due to pathologic frx, osteomyelitis, or DJD;
            - type II::
                    - acute neuropathic form;
                    - most patients don't survive more than 9 months;
            - type III:
                    - sub acute neuronopathic;
                    - convulsions are frequent;

- Clinical Presentation:
     - bone crises (episodes of pain and swelling), sometimes accompanied by fever but w/o x-ray changes, are common, recurrent
            manifestations of the disease.
            - often the pain cannot be controled w/ narcotics;
            - pain may last days or several weeks;
     - AVN of the femoral head
            - is often the most symptomatic lesion;
            - bilateral disease is common;
     - hypersplenism:
            - spleen may become enormous and splenic infarcts are common;
            - pancytopenia w/ severe thrombocytopenia is seen;
            - splenectomy offers temporary relief but pancytopenia may recur w/ depletion of the normal marrow elements;

- Radiographs:
     - fusiform enlargement of distal metaphyseal area of femur w/ incomplete tubulation & radiolucent areas;
     - flaring of distal femur (Erlenmeyer-flask deformity), is classic sign;
             - note that the "flask" deformity is also found in Niemann-Pick disease and osteopetrosis;
             - Niemann Pick disease is associated w/ severe mental retardation (and therefore should not be confused w/ Gaucher's disease);
             - osteopetrosis has a characteristic appearance (hence should not be confused w/ Gaucher's);
     - look for bone destruction, sclerosis, & periosteal new bone form formation in femoral shaft in bone crisis or pseudoosteomyeltic form;
     - aseptic necrosis of femoral heads, bone infarcts, & pathologic frx of long bone are all frequent complications;
     - references:
             - Image Challenge: NEJM

- MRI:
     - decreased T2 signal is seen in the marrow of long bones, vertebrae, & hips and is related to the areas of marrow infiltrated by Gaucher's lipids;

- Treatment:
     - b-glucosidase mannose substitution:
           - mannose substitution to the enzyme glucosidase allows it to enter macrophages and destroy lipid;
           - destroys the accumulated glucocerebroside in the lysosomal body;

     - pathologic frx:
           - frx related to pathologic weakening of skeleton secondary to Gaucher's involvment are best treated conservatively;
                  - frxs are esp common in young children;
           - frx proximal end of femur may occur in children & adults;
                  - these may be treated non operatively although there may be w/ some varus deformity;
     - bone crisis:
           - most patients are managed w/ brief bed rest and analgesics, which is followed by crutches as tolerated;
     - AVN:
           - no effective treatment or preventative measures;
           - most patients are managed w/ brief bed rest and analgesics which is followed by crutches as tolerated;
     - total hip replacement:
               - increased risks of infection & bleeding
               - increased loosening of prosthetic components


Bone Scans in the Diagnosis of Bone Crisis in Patients Who Have Gaucher Disease.

Review Article: Current Concepts: Gaucher's Disease.

Total hip replacement in Gaucher's disease.

Hip arthroplasties in Gaucher's disease.

Total hip arthroplasty in Gaucher's disease. Long-term prognosis.

The natural history of osteonecrosis of the femoral head in children and adolescents who have Gaucher disease.

Original Text by Clifford R. Wheeless, III, MD.

Last updated by Data Trace Staff on Tuesday, September 12, 2017 7:25 am