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Outcome of partial splenectomy for type I Gaucher disease
596
Zimran et al.
The Journal of Pediatrics April 1995
Outcome of partial splenectomy for type I Gaucher disease A. Zimran, MD, D. Elstein, PhD, R. S c h i f f m a n n , MD, A. A b r a h a m o v , MD, M. Goldberg, MD, J, A. Bar-Maor, MD, R. O. Brady, MD, P. C. Guzzetta, MD, a n d N. W. Barton, MD, PhD From the Gaucher Clinic and Department of Surgery A, Shaare Zedek Medical Center, Jerusalem, and the Department of Pediatric Surgery, Rambam Medical Center, Haifa, Israel; the Developmental and Metabolic Neurology Branch, National Institutes of Health, Bethesda, Maryland; and the Division of Pediatric Surgery, University of Texas, Southwestern Medical Center, Dallas
Partial splenectomy was introduced to achieve the benefits of splenectomy and to avoid the risk of overwhelming infection in patients with symptomatic Gaucher disease. We observed regrowth of the splenic remnant, reemergence of preoperative symptoms, and new bone involvement a m o n g most of our patients who had undergone partial splenectomy. Enzyme replacement therapy has markedly limited indications for splenectomy, partial or total, for Gaucher disease. (J PEDIATR1995;126:596-7) The majority of patients with symptomatic Gaucher disease have splenic enlargement, which may be enormous, causing thrombocytopenia, anemia, abdominal discomfort with early satiety, severe abdominal pain associated with infarcts, and mechanical interference with adjoining organs. 1 Until the recent introduction of enzyme replacement therapy, 2 surgical removal of the spleen was a common therapeutic procedure to correct the hematologic abnormalities and to relieve the symptoms of mechanical compression. 1 Partial splenectomy was suggested as a means of reversing the hematologic and mechanical complications of splenomegaly while reducing the risk of overwhelming infection. 3 Recent reports have noted fewer secondary complications in patients who had undergone partial splenectomy relative to those in patients who had had total splenectomy. 46 We describe our experience with long-term clinical outcome in 24 patients with type I Gaucher disease who have undergone partial splenectomy. METHODS
All our patients with Gaucher disease who had undergone partial splenectomy were included; 16 were from Israel and 8 from Washington, D.C. Indications for partial splenectomy included severe hypersplenism and mechanical complications resulting from massive enlargement of the spleen.
Submitted for publication July l, 1994; accepted Nov. 8, 1994. Reprint requests: Ari Zimran, MD, Gaucher Clinic, Shaare-Zedek Medical Center, P.O. Box 3235, Jerusalem 91031, Israel. 9/22/61902
There were 17 female and 7 male patients. Age at partial splenectomy ranged between 6 and 48 years; 17 patients were less than 18 years of age. The patients have been followed for up to 13 years after partial splenectomy (mean follow-up, 7.3 years). Seven other patients were not included in the current survey because they required emergency total splenectomy because of bleeding within 24 hours of partial splenectomy. RESULTS In 21 (87.5%) of the 24 patients significant regrowth of the splenic remnant developed with reemergence of all presurgical symptoms, and total splenectomy or enzyme replacement therapy was required after partial splenectomy. Mild to moderate bone involvement was present in seven patients (29%) preoperatively. During postsurgical follow-up (often <3 years), new bone-related complications, including avascular necrosis of the hip joints in nine patients (37.5%), developed in 12 patients (50%). The severity of the previous skeletal involvement progressed in six of seven patients; in two of these patients, avascular necrosis developed. Progression occurred in both children and adults. Six patients (25%) were free of bone-related symptoms during their follow-up period. DISCUSSION Partial splenectomy was associated with a higher risk of postoperative bleeding complications relative to total splenectomy and with eventual regrowth of the residual spleen and reestablishment of all original symptoms in our patients with Gaucher disease. Seven patients required emergency
The Journal of Pediatrics Volume 126, Number 4
total splenectomy and multiple blood transfusions. Regrowth of the splenic remnant occurred in 21 of our 24 patients and in all seven patients described by Cohen et al. 6 Fleshner et al. 5 described an 18-month-old girl in whom rapid regrowth of the splenic remnant developed; she required splenectomy and then bone marrow transplantation but died 21 months later. Enzyme replacement therapy may decrease spleen volume by 50% to 75% within the first 2 years of treatment; thus the rationale for splenectomy should be reevaluated. In addition, Pastores et al. 7 and Zimran et al. 8 reported comparable responses to enzymatic treatment in patients with or without a spleen; consequently, there appears to be no role for splenectomy, either total or partial, as a preparatory procedure to enhance the clinical response to enzyme replacement therapy. Our suggestions for the indications for splenectomy in the era of enzyme replacement therapy are limited to the following very specific situations: ( 1) when enzyme replacement is not a suitable option (e.g., where the cost is prohibitive), (2) life-threatening thrombocytopenia or a critical need for surgery (such as coronary bypass) in a patient with a very low platelet count, (3) inferior vena cava syndrome, (4) unremitting abdominal pain resulting from recurrent splenic infarction, and (5) severe restrictive pulmonary disease with incipient respiratory failure. Under these circumstances we prefer total splenectomy in adults or
ROtig et al.
adolescents but may consider partial splenectomy in children less than 6 years of age. REFERENCES
1. Zimran A, Kay A, Gelbart T et al. Gaucher disease: clinical, laboratory, radiologic and genetic features of 53 patients. Medicine 1992;71:337-53. 2. Barton NW, Brady RO, Dambrosia JM, et al. Replacement therapy for inherited enzymedeficiency:macrophage-targeted glucocerebrosidasefor Gaucher's disease; N Engl J Med 1991; 325:1464-70. 3. Beutler E. Newer aspects of some interesting lipid storage diseases: Tay-Sachs and Gaucher disease. West J Med 1977; 126:46-54. 4. Guzzetta PC, Riley EJ, Merrick HFW, Verderese C, Barton N. Electivesub-total splenectomy:indicationsand results in 33 patients. Ann Surg 1990;211:34-42. 5. Fleshner PR, Aufsus AH Jr, Grabowski GA. A 27 year experience with splenectomy for Gaucher's disease. Am J Surg 1991; 161:69-75. 6. Cohen IJ, Katz K, Freud E, Zer M, Zaizov R. Long-term follow-upof partial splenectomyin Gaucher's disease. Am J Surg 1992;164:345-7. 7. Pastores GM, Sibille AR, Grabowski GA. Enzyme therapy in Gaucher disease type I: dosage, efficacyand adverse effects in 33 patients treated for 6 to 24 months. Blood 1993;82:408-16. 8. Zimran A, Elstein D, Kannai R, et al. Low-dose enzyme replacement therapy for Gaucher's disease: effects of age, sex, genotype and clinical features on responseto treatment: Am J Med 1194;97:3-13.
Deletion of mitochondrial DNA in patient with chronic tubulointerstitial nephritis A g n 6 s ROtig, PhD, Fran(~oise Goutieres, MD, Patrick N i a u d e t , MD, Pierre Rustin, Phb, D o m i n i q u e C h r e t i e n , PhD, G e n e v i 6 v e Guest, MD, J a c q u e l i n e Mikol, MD, M a r i e - C l a i r e Gubler, MD, a n d Arnold Munnich, MD, PhD From the Unit6 de Recherches sur tes Handicaps G6n~tiques de I'Enfant INSERMU393, Unit6 de Recherches de N6phrologie P6diatrique, INSERMU~92 and D~partement de P6diatrie, H6pital des Enfants-Malades, Paris, France, and the Service d'Anatomopathologie, H(~pital Lariboisi~re, Paris, France
We report a mitochondrial DNA deletion (2.6 kb) in a boy with tubulointerstitial nephritis in whom chronic renal failure and leukodystrophy subsequently developed. Elevated lactate values in plasma and cerebrospinal fluid were
Submitted for publication July 26, 1994; accepted Oct. 24, 1994. Reprint requests: Arnold Munnich, MD, INSERM U393, H6pital des Enfants Malades, 149 rue de S~vres, 75743 Paris-Cedex 15, France.
597
Copyright ® 1995 by Mosby-Year Book, Inc. 0022-3476/95/$3.00 + 0 9/22/61435
Zimran et al.
The Journal of Pediatrics April 1995
Outcome of partial splenectomy for type I Gaucher disease A. Zimran, MD, D. Elstein, PhD, R. S c h i f f m a n n , MD, A. A b r a h a m o v , MD, M. Goldberg, MD, J, A. Bar-Maor, MD, R. O. Brady, MD, P. C. Guzzetta, MD, a n d N. W. Barton, MD, PhD From the Gaucher Clinic and Department of Surgery A, Shaare Zedek Medical Center, Jerusalem, and the Department of Pediatric Surgery, Rambam Medical Center, Haifa, Israel; the Developmental and Metabolic Neurology Branch, National Institutes of Health, Bethesda, Maryland; and the Division of Pediatric Surgery, University of Texas, Southwestern Medical Center, Dallas
Partial splenectomy was introduced to achieve the benefits of splenectomy and to avoid the risk of overwhelming infection in patients with symptomatic Gaucher disease. We observed regrowth of the splenic remnant, reemergence of preoperative symptoms, and new bone involvement a m o n g most of our patients who had undergone partial splenectomy. Enzyme replacement therapy has markedly limited indications for splenectomy, partial or total, for Gaucher disease. (J PEDIATR1995;126:596-7) The majority of patients with symptomatic Gaucher disease have splenic enlargement, which may be enormous, causing thrombocytopenia, anemia, abdominal discomfort with early satiety, severe abdominal pain associated with infarcts, and mechanical interference with adjoining organs. 1 Until the recent introduction of enzyme replacement therapy, 2 surgical removal of the spleen was a common therapeutic procedure to correct the hematologic abnormalities and to relieve the symptoms of mechanical compression. 1 Partial splenectomy was suggested as a means of reversing the hematologic and mechanical complications of splenomegaly while reducing the risk of overwhelming infection. 3 Recent reports have noted fewer secondary complications in patients who had undergone partial splenectomy relative to those in patients who had had total splenectomy. 46 We describe our experience with long-term clinical outcome in 24 patients with type I Gaucher disease who have undergone partial splenectomy. METHODS
All our patients with Gaucher disease who had undergone partial splenectomy were included; 16 were from Israel and 8 from Washington, D.C. Indications for partial splenectomy included severe hypersplenism and mechanical complications resulting from massive enlargement of the spleen.
Submitted for publication July l, 1994; accepted Nov. 8, 1994. Reprint requests: Ari Zimran, MD, Gaucher Clinic, Shaare-Zedek Medical Center, P.O. Box 3235, Jerusalem 91031, Israel. 9/22/61902
There were 17 female and 7 male patients. Age at partial splenectomy ranged between 6 and 48 years; 17 patients were less than 18 years of age. The patients have been followed for up to 13 years after partial splenectomy (mean follow-up, 7.3 years). Seven other patients were not included in the current survey because they required emergency total splenectomy because of bleeding within 24 hours of partial splenectomy. RESULTS In 21 (87.5%) of the 24 patients significant regrowth of the splenic remnant developed with reemergence of all presurgical symptoms, and total splenectomy or enzyme replacement therapy was required after partial splenectomy. Mild to moderate bone involvement was present in seven patients (29%) preoperatively. During postsurgical follow-up (often <3 years), new bone-related complications, including avascular necrosis of the hip joints in nine patients (37.5%), developed in 12 patients (50%). The severity of the previous skeletal involvement progressed in six of seven patients; in two of these patients, avascular necrosis developed. Progression occurred in both children and adults. Six patients (25%) were free of bone-related symptoms during their follow-up period. DISCUSSION Partial splenectomy was associated with a higher risk of postoperative bleeding complications relative to total splenectomy and with eventual regrowth of the residual spleen and reestablishment of all original symptoms in our patients with Gaucher disease. Seven patients required emergency
The Journal of Pediatrics Volume 126, Number 4
total splenectomy and multiple blood transfusions. Regrowth of the splenic remnant occurred in 21 of our 24 patients and in all seven patients described by Cohen et al. 6 Fleshner et al. 5 described an 18-month-old girl in whom rapid regrowth of the splenic remnant developed; she required splenectomy and then bone marrow transplantation but died 21 months later. Enzyme replacement therapy may decrease spleen volume by 50% to 75% within the first 2 years of treatment; thus the rationale for splenectomy should be reevaluated. In addition, Pastores et al. 7 and Zimran et al. 8 reported comparable responses to enzymatic treatment in patients with or without a spleen; consequently, there appears to be no role for splenectomy, either total or partial, as a preparatory procedure to enhance the clinical response to enzyme replacement therapy. Our suggestions for the indications for splenectomy in the era of enzyme replacement therapy are limited to the following very specific situations: ( 1) when enzyme replacement is not a suitable option (e.g., where the cost is prohibitive), (2) life-threatening thrombocytopenia or a critical need for surgery (such as coronary bypass) in a patient with a very low platelet count, (3) inferior vena cava syndrome, (4) unremitting abdominal pain resulting from recurrent splenic infarction, and (5) severe restrictive pulmonary disease with incipient respiratory failure. Under these circumstances we prefer total splenectomy in adults or
ROtig et al.
adolescents but may consider partial splenectomy in children less than 6 years of age. REFERENCES
1. Zimran A, Kay A, Gelbart T et al. Gaucher disease: clinical, laboratory, radiologic and genetic features of 53 patients. Medicine 1992;71:337-53. 2. Barton NW, Brady RO, Dambrosia JM, et al. Replacement therapy for inherited enzymedeficiency:macrophage-targeted glucocerebrosidasefor Gaucher's disease; N Engl J Med 1991; 325:1464-70. 3. Beutler E. Newer aspects of some interesting lipid storage diseases: Tay-Sachs and Gaucher disease. West J Med 1977; 126:46-54. 4. Guzzetta PC, Riley EJ, Merrick HFW, Verderese C, Barton N. Electivesub-total splenectomy:indicationsand results in 33 patients. Ann Surg 1990;211:34-42. 5. Fleshner PR, Aufsus AH Jr, Grabowski GA. A 27 year experience with splenectomy for Gaucher's disease. Am J Surg 1991; 161:69-75. 6. Cohen IJ, Katz K, Freud E, Zer M, Zaizov R. Long-term follow-upof partial splenectomyin Gaucher's disease. Am J Surg 1992;164:345-7. 7. Pastores GM, Sibille AR, Grabowski GA. Enzyme therapy in Gaucher disease type I: dosage, efficacyand adverse effects in 33 patients treated for 6 to 24 months. Blood 1993;82:408-16. 8. Zimran A, Elstein D, Kannai R, et al. Low-dose enzyme replacement therapy for Gaucher's disease: effects of age, sex, genotype and clinical features on responseto treatment: Am J Med 1194;97:3-13.
Deletion of mitochondrial DNA in patient with chronic tubulointerstitial nephritis A g n 6 s ROtig, PhD, Fran(~oise Goutieres, MD, Patrick N i a u d e t , MD, Pierre Rustin, Phb, D o m i n i q u e C h r e t i e n , PhD, G e n e v i 6 v e Guest, MD, J a c q u e l i n e Mikol, MD, M a r i e - C l a i r e Gubler, MD, a n d Arnold Munnich, MD, PhD From the Unit6 de Recherches sur tes Handicaps G6n~tiques de I'Enfant INSERMU393, Unit6 de Recherches de N6phrologie P6diatrique, INSERMU~92 and D~partement de P6diatrie, H6pital des Enfants-Malades, Paris, France, and the Service d'Anatomopathologie, H(~pital Lariboisi~re, Paris, France
We report a mitochondrial DNA deletion (2.6 kb) in a boy with tubulointerstitial nephritis in whom chronic renal failure and leukodystrophy subsequently developed. Elevated lactate values in plasma and cerebrospinal fluid were
Submitted for publication July 26, 1994; accepted Oct. 24, 1994. Reprint requests: Arnold Munnich, MD, INSERM U393, H6pital des Enfants Malades, 149 rue de S~vres, 75743 Paris-Cedex 15, France.
597
Copyright ® 1995 by Mosby-Year Book, Inc. 0022-3476/95/$3.00 + 0 9/22/61435