Abstract
In 1882, as a French medical student, Philippe Charles Ernest Gaucher, described a 32 year old female with an enlarged spleen that he thought was an epithelioma.
Gaucher disease, the most prevalent lysosomal storage disorder, is a result of a genetic defect in the enzyme β-glucocerebrosidase (EC3.2.1.45), and the consequent accumulation of a glycolipid, glucocerebroside, in the cells of the monocyte-macrophage system, the “Gaucher cells”.
Of more than 200 mutations identified, most are private or rare mutations; those with some prevalence have been loosely categorized as a mild, severe, or lethal mutations on the basis of residual enzyme and clinical phenotype.
The most common presentation includes hepato-splenomegaly, anemia, and thrombocytopenia. Bone involvement is perhaps the most variable of all the findings attributed to Gaucher disease: ranging from asymptomatic disease, with or without radiological signs, to symptomatic disease, including avascular necrosis of bone adjacent to the large joints and pathological fractures (including compressed fractures of the spine). Episodic “crises” of bone pain in children and young adults, are common manifestations, which can be severe and engender considerable pain and disability.
One feature of Gaucher disease is the failure of correlation of bone with visceral or hematological disease. Symptomatic bone disease, may occur in any patient regardless of the extent of the visceral manifestations, and may be present or relatively absent in patients with severe splenomegaly or bone marrow depression.
With the advent of enzyme replacement therapy (ERT), which has proven to be safe and effective in improving the hematological parameters and reducing the organomegaly, it was hoped that the bone disease would be equally amenable to replacement therapy. But, the general experience has been that the skeletal response is considerably slower. However, it does seem that bone crises are much less frequent among ERT-treated patients. The greatest advantage of ERT to the skeleton is prevention before irreversible damage occurs, and that severe skeletal complications are usually prevented if ERT is begun at an early age in patients at risk. In addition, because of cost considerations, many national health budgets are unable to acquire ERT for affected patients and these individuals continue to suffer from the consequences of the natural history of their disease. Thus, the need for orthopaedic consultations and interventions are as critical today as in the era prior to global marketing of ERT.
This lecture outlines findings from the large referral clinic (> 500 patients) in the decade since the advent of specific enzyme replacement therapy. Although there have been some theories suggested to explain aspects of the pathological behavior of Gaucher bone, no one model is completely adequate: much is poorly understood. We face a relatively young and intelligent patient population whose expectations of quality of life are high and most patients do not want to be restricted in their daily activities. On the other hand, there arises the question whether conventional orthopaedic solutions, such as osteotomies, joint replacements or arthrodesis will be as successful as in patients with normal bones, this was the goal of our investigations.
The abstracts were prepared by Orah Naor, IOA Co-ordinator and Secretary. Correspondence should be addressed to Israel Orthopaedic Association, PO Box 7845, Haifa 31074, Israel.
