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Letters to the Editor

Indian Pediatrics 2001; 38: 686-688  

Enzyme Replacement Therapy in Gaucherís Disease


Gaucherís disease is the most prevalent lysosomal storage disease due to deficiency of glucocerebrosidase (GCR) activity with secondary accumulation of GCR within the lysosomes of macrophages. This storage disorder produces characteristically multi-system abnormalities such as visceral enalrgement and structural skeletal changes. Enzyme replacement therapy is the treatment of choice.

A two-year-old male child was brought to us for severe pallor and abdominal distention. On clinical examination he had severe anemia, growth failure, and massive spleno-megaly of 15 cm and hepatomegaly of 2.5 cm with no neurological and skeletal involve-ment. Investigations showed hemoglobin of 4.5 g/dl with pancytopenia and normal pattern of hemoglobin electrophoresis. Bone marrow aspiration showed collection of histiocytes with abundant sea-blue cytoplasm suggestive of Gaucherís disease. Blood was sent to Willink Biochemical Genetics Unit, U.K. for enzyme assay. There was marked reduction of b-glucosidase activity with marked elevation of chitotriosidase activity in plasma, confirming the diagnosis of Gaucherís disease.

In view of splenohepatomegaly, and reduction of b-glucosidase activity with no neurological involvement, a diagnosis of type I Gaucherís disease was made. For the subse-quent three years without blood transfusion his hemoglobin was maintained between 8 to 9 g/dl and he had mild leukopenia and thrombocytopenia. During this period his spleen progressively increased in size upto 24 cm and liver size upto 14 cm. Splenectomy was performed to prevent splenic rupture and to relieve mechanical burden.

Intravenous enzyme replacement therapy with GCR was started postoperatively. The enzyme GCR is available as treatment for Gaucherís disease since the early 1990ís. It is extracted from human placentas (Ceredase) or generated in the laboratory by recombinant technique (Cerezyme) and then chemically modified to target it to macrophages(1). Barton et al. recommend dosage of 60 units/kg body weight per infusion every two weeks till the patient is stabilized. The dose can be halved every six months until the minimum needed for biochemical control is determined, possibly 7.5 to 15 IU per kilogram every two-weeks(2). We are following this regimen in our patient. He was getting 40 units/Kg biweekly for six months and now he is maintained on 20 units/Kg. The child has completed one year of treatment and his growth and hematological parameters are normal. Liver size has regressed from 14 cm to 1 cm below the costal margin.

Enzymes are supplied by Genzyme Cor-poration on the basis of "Gaucher Humani-tarian Initiative" program designed to help seriously ill Gaucherís patients. Intravenous replacement of the enzyme Ceredase in type I Gaucherís patients dramatically reverses the signs of illness in receipients regardless of genotype(3).

Ceredase is very expensive. The price of 1 IU of ceredase is $3.50. If it is given in the dose of 60 units/Kg once every two weeks which is called "high dose low-frequency protocol", the cost of treating a child who weighs 35 kg would be $ 191,100 per year for the drug alone(3). In an attempt to reduce the cost, without compromising the efficacy of the treatment, Beutler et al. have proposed the administration of smaller doses at a higher frequency, 30 units/kg/month, fractionated to equal doses, three times per week. The effi-cacy of low-dose treatment was just as satisfactory as that of "high-dose low-frequency protocol"(4). It also reduces the cost by $6,000 per week approximately. However, the intravenous administration of the enzyme three times a week creates a major burden on both patient and close family members(4). When cost is not an issue, the high-dose/low-frequency protocol may be the regimen of choice, mainly because of its convenience. As long as cost continues to play a major role, the low-dose/high-fre-quency protocol seems to be the right one(5). Low-dose/low-frequency imiglucerase (the recombinant enzyme) may be an alternative approach with satisfactory clinical response and uncompromised quality of life(6). For detecting carriers, amniocentesis and chorio-nic villi sampling (CVS) can be used to diagnose disease early in pregnancy.

L. Kasturi,
Amin Alpa S.,
Department of Pediatrics, BARC Hospital,
, Mumbai 400 094, India.


1. Bembi B, Zanatta M, Carrozzi M, Baralle F, Gornati R, Berra B, et al. Enzyme replacement treatment in type 1 and type 3 Gaucherís disease. Lancet 1994; 344: 1669-1682.

2. Barton NW, Brady RO, Murray GJ, Argoff CE, Grewal RP, Kian-Ti Yu, et al. Enzyme replacement therapy for Gaucherís disease. N Engl J Med 1991; 325: 1811.

3. Barton NW, Oí Brady R, Dambrosia JM, Bisceglie MA, Doppelt SH, Hill C et al. Replacement therapy for inherited enzyme deficiency: Macrophage targeted glucoc-erebrosidase for Gaucherís disease. N Engl J Med 1991; 324: 1464-1470.

4. Zimran A, Hadas-Halpern I, Zevin S, Levy-lahad E, Abrahamov A. Low-dose high frequency enzyme replacement therapy for young children with severe Gaucher disease. Br J Hematol 1993; 85: 763-786.

5. Zimran A, Elstein D, Kannai R, Zevin S, Hadas-Halpern I, Levy-Lahad E, et al. Low-dose enzyme replacement therapy for Gaucherís disease: Effects of age, sex, geno-type and clinical features on response to treatment. Am J Med 1994; 97: 3-13.

6. Zimran A, Elstein D, Levy-Lahad E, Zevin S, Hadas-Halpern I, Bar-Ziv Y, et al. Replace-ment therapy with imiglucerase for type I Gaucherís disease. Lancet 1995; 345: 1479-1480.


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