population leading to an estimated birth frequency of 1 in 1400. There are about 30,000 
patients in the United States with type 1 Gaucher’s disease. While more than 25 
mutations of the GC gene have been described, five specific mutations at nucleotide 
1226, 84, 1448, 1297 and in intron 2 account for more than 97.5% of all cases in this 
population. 
Clinical presentation of type 1 Gaucher’s disease has a later onset with the average 
beginning of symptomatic disease at 25 years of age. The most common initial acute 
clinical presentations are bleeding manifestations resulting from increased thrombocyte 
sequestration in the enlarged spleen. Hepatic enlargement may become 
hemodynamically relevant leading to liver fibrosis and portal shunting with the 
development of varices and shunting through the lung. The most common 
manifestations of Gaucher’s disease in the bone are lytic widening of the distal femurs, 
avascular necrosis of the femoral head, widening of the humeri, sclerosis and infarcts of 
the long bones and joint surfaces and other types of lytic lesions. Excruciating pain is 
the most troublesome of Gaucher’s disease bone manifestations. It can occur anywhere 
in the skeleton, can be very severe and last for weeks or months. Compression fractures 
of the spinal vertebrae may occur. While ongoing organomegaly can be symptomatic in 
the form of abdominal discomfort and pain, liver failure with subsequent bleeding 
complications, and bone problems are the major cause of chronic morbidity in type 1 
Gaucher’s disease patients. 
The diagnosis of type 1 Gaucher’s disease is suspected based on genetic descent and 
presenting symptoms. It is established by demonstration of leukocyte glucocerebrosidase 
deficiency. Most patients have readily demonstrable Gaucher’s cells in their bone 
marrow biopsy. The presence of these glucocerebroside-laden macrophages with 
characteristic striatae, inclusion bodies, an eccentrically located nucleus and a PAS- 
positive cytoplasm is a sign of disease activity. Therapy options in type 1 Gaucher’s 
disease can be divided into symptomatic and curative approaches. Symptomatic 
treatments include those directed toward improvement of hematologic and bony 
manifestations. Thrombocytopenia and leukopenias, as well as other symptoms of 
organomegaly improve after splenectomy, however, this treatment has been associated 
with accelerated progression of bone disease by removing the major storage organ for 
the accumulating glucocerebroside. Bone lesions can be treated with orthopedic surgery 
such as hip joint replacements and pain therapy. None of these options have any 
influence on the underlying disease. In order to limit the disease progression and 
reverse some of its manifestations, a source of macrophage glucocerebrosidase activity 
must be provided. Two curative options have been clinically used to date. These 
include marrow transplantation and exogenous enzyme supplementation. 
Transplantation of marrow from an HLA-identical sibling has been demonstrated to 
repopulate the recipient RES with normal macrophages and led to the disappearance of 
Gaucher’s cells in the RES, as well as reversing the organomegaly (5-9). However, a 
matched family donor is available for only about 25% of patients. Furthermore, bone 
marrow transplantation has a procedure-related mortality that may not be a justifiable 
risk in patients with chronic or slowly progressing non-neuronopathic Gaucher’s disease. 
Enzyme replacement therapy with macrophage targeted glucocerebrosidase has been 
recently feasible (10-13). Through a process of large-scale purification and sequential 
deglycosylation of the native enzyme, the resulting alglucerase (ceredase) is taken up 
[662] 
Recombinant DNA Research, Volume 18 
