What are the skeletal manifestations of Gaucher disease?
Gaucher disease is caused by autosomal recessive inheritance of a deficiency of glucocerebrosidase that affects 1 in 20,000 births and is caused by one of 300 mutant alleles of the gene encoding this enzyme, located on chromosome 1. Type I (adult form) is the most common of the three forms and occurs most commonly in Ashkenazi Jews. The enzyme deficiency leads to accumulation of glucosylceramide within macrophages (Gaucher cells). Splenomegaly with hypersplenism is the most common presenting manifestation. Hepatomegaly occurs later, as does pulmonary involvement (interstitial lung disease, pulmonary hypertension). Skeletal involvement occurs in 50% to 85% of patients, including long bone or hip/shoulder pain from osteonecrosis and bony infarctions, as well as back pain from osteoporosis with fractures. Bone crisis (10%) can cause acute pain and swelling associated with elevated acute-phase reactants. Radiographic abnormalities are seen in 80% to 95% of patients and include osteopenia, osteolytic lesions, bony infarcts with serpiginous osteosclerotic areas, distal femur deformity (Erlenmeyer flask), H-shaped vertebrae, and osteonecrosis of the femoral and humeral heads and femoral condyles. The diagnosis is suspected by demonstrating Gaucher cells on bone marrow biopsy and confirmed by measuring enzyme activity in circulating lymphocytes. Three infused glucocerebrosidases (imiglucerase [Cerezyme], velaglucerase alfa [VPRIV], and taliglucerase alfa [Elelyso]) are available for enzyme replacement therapy. Alternatively, there are two oral medications (miglustat [Zayesca] and eligustadt [Cerdelga]), which decrease substrate synthesis resulting in less glucosylceramide accumulation. The annual cost of these oral or infused therapies is $300,000. Symptomatic therapy includes bisphosphonates, analgesics, splenectomy, and joint replacement. Bone marrow transplantation has also been successful.
