Case 20-2003: Gaucher's Disease
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《新英格兰医药杂志》
To the Editor: In discussing the case of a girl with hepatosplenomegaly and pain in the thigh (June 26 issue),1 Larsen arrived at the diagnosis of Gaucher's disease, and he correctly points out that Gaucher's disease can be diagnosed by assaying leukocyte -glucosidase levels. But it is inappropriate to suggest that histologic demonstration of Gaucher's cells is either an alternative or a more expeditious approach. It is perhaps more expeditious for the physician, but it is hardly so for the patient.2
The patient in the current case had a good response to enzyme-replacement therapy at the more-than-ample dose of 60 U per kilogram of body weight per month. Sometimes, during the first year of high-dose enzyme-replacement therapy, new fractures do develop.3 Pain from such fractures is not an indication for a dose increase. There is no relationship between the disappearance of bone pain and the dose of enzyme, and the pain due to fractures generally abates spontaneously as healing occurs. For a 40-kg patient, the annual cost of treatment with 60 U per kilogram per month is about $116,000 per year. In the current case, the unnecessary doubling of the dosage, apparently triggered by pain due to a fracture, probably added $116,000 annually to the cost.
Ernest Beutler, M.D.
Scripps Research Institute
La Jolla, CA 92037
beutler@scripps.edu
References
Case Records of the Massachusetts General Hospital (Case 20-2003). N Engl J Med 2003;348:2669-2677.
Beutler E, Saven A. Misuse of marrow examination in the diagnosis of Gaucher disease. Blood 1990;76:646-648.
Beutler E, Demina A, Laubscher K, et al. The clinical course of treated and untreated Gaucher disease: a study of 45 patients. Blood Cells Mol Dis 1995;21:86-108.
The discussants reply: In this child with severe pain, whom we suspected had Gaucher's disease, we believed it was important to establish the diagnosis quickly and to initiate treatment. Therefore, we performed bone marrow biopsies, which gave us an answer in 24 hours. The results of the -glucosidase assay were received two weeks later and confirmed the diagnosis.
We increased the enzyme-replacement dose when the patient did not have a response, in our opinion, to the initial dose. Her pain altered her gait and her ability to ambulate and necessitated the use of crutches. Radiographic studies documented worsening bone disease, with avascular necrosis of both femoral heads and collapse, growth arrest, and shortening of the right femoral neck. The increase in dosage was followed over the next few months by cessation of pain and restoration of a normal gait.
The patient's hematologic values and organomegaly have improved, but the chitotriosidase level remains elevated, at more than 4000 nmol per hour per milliliter (normal value, <65), and the spleen remains enlarged. We continue therapy at a dose of 120 U per kilogram of body weight biweekly, with close monitoring, and will reduce the dose as tolerated.
Katherine Sims, M.D.
David Ebb, M.D.
Massachusetts General Hospital
Boston, MA 02114
The patient in the current case had a good response to enzyme-replacement therapy at the more-than-ample dose of 60 U per kilogram of body weight per month. Sometimes, during the first year of high-dose enzyme-replacement therapy, new fractures do develop.3 Pain from such fractures is not an indication for a dose increase. There is no relationship between the disappearance of bone pain and the dose of enzyme, and the pain due to fractures generally abates spontaneously as healing occurs. For a 40-kg patient, the annual cost of treatment with 60 U per kilogram per month is about $116,000 per year. In the current case, the unnecessary doubling of the dosage, apparently triggered by pain due to a fracture, probably added $116,000 annually to the cost.
Ernest Beutler, M.D.
Scripps Research Institute
La Jolla, CA 92037
beutler@scripps.edu
References
Case Records of the Massachusetts General Hospital (Case 20-2003). N Engl J Med 2003;348:2669-2677.
Beutler E, Saven A. Misuse of marrow examination in the diagnosis of Gaucher disease. Blood 1990;76:646-648.
Beutler E, Demina A, Laubscher K, et al. The clinical course of treated and untreated Gaucher disease: a study of 45 patients. Blood Cells Mol Dis 1995;21:86-108.
The discussants reply: In this child with severe pain, whom we suspected had Gaucher's disease, we believed it was important to establish the diagnosis quickly and to initiate treatment. Therefore, we performed bone marrow biopsies, which gave us an answer in 24 hours. The results of the -glucosidase assay were received two weeks later and confirmed the diagnosis.
We increased the enzyme-replacement dose when the patient did not have a response, in our opinion, to the initial dose. Her pain altered her gait and her ability to ambulate and necessitated the use of crutches. Radiographic studies documented worsening bone disease, with avascular necrosis of both femoral heads and collapse, growth arrest, and shortening of the right femoral neck. The increase in dosage was followed over the next few months by cessation of pain and restoration of a normal gait.
The patient's hematologic values and organomegaly have improved, but the chitotriosidase level remains elevated, at more than 4000 nmol per hour per milliliter (normal value, <65), and the spleen remains enlarged. We continue therapy at a dose of 120 U per kilogram of body weight biweekly, with close monitoring, and will reduce the dose as tolerated.
Katherine Sims, M.D.
David Ebb, M.D.
Massachusetts General Hospital
Boston, MA 02114