Correspondence
Hydroxyurea in Congenital Erythropoietic Porphyria
N Engl J Med 1994; 330:1091-1092April 14, 1994
- Article
To the Editor:
Congenital erythropoietic porphyria is a defect of uroporphyrinogen III synthase, with accumulation of uroporphyrin I, extreme hemolysis, and photosensitivity1,2. We previously reported the effectiveness of aggressive transfusion in a patient with severe disease3. The excess porphyrins were mostly of erythropoietic origin.
The patient, who had been dependent on transfusions since birth, is now 18 years old. The base-line hematocrit, maintained initially at 20 percent or higher, was raised to 33 percent or higher by two years of age. The serum porphyrin levels remained at 48 to 76 μg per deciliter. At the age of six years, the base-line hematocrit was raised to 39 percent or higher. The serum porphyrin levels dropped to normal values (<2 μg per deciliter), and the symptoms disappeared3. At the age of seven, a splenectomy was performed. Assiduous deferoxamine therapy since the age of three had maintained the serum ferritin levels at 800 to 1100 ng per milliliter, which is above the normal range (15 to 400 ng per milliliter) but below the levels observed in patients with severe iron overload.
At the age of 14, during puberty, the serum porphyrin levels increased ( ≤ 15 μg per deciliter) but without the appearance of symptoms. At the age of 15, the serum porphyrin levels were up to 60 μg per deciliter, and skin vesicles reappeared. The base-line hematocrit was increased to more than 41 percent, with no effect. Since photosensitivity had worsened, hydroxyurea was given (Figure 1Figure 1
Changes in the Serum Porphyrin Level and Platelet Count during Treatment with Hydroxyurea in a Patient with Congenital Erythropoietic Porphyria.), on the basis of the experience with this therapy in polycythemia vera4. Hydroxyurea was administered in equal oral doses on four consecutive days, followed by a three-day interval, at a dose of 2 g per week, and the dose was slowly increased to 10 g per week. The serum porphyrin levels decreased (<10 μg per deciliter), but the platelet count also decreased, to below 100,000 per cubic millimeter. Hydroxyurea treatment was stopped; the serum porphyrin levels rebounded (>50 μg per deciliter), and the platelet count increased. Hydroxyurea was then reinstituted at a dose of 8 g per week; the serum porphyrin levels remained under 20 μg per deciliter, without photosensitivity, and the platelet count remained over 130,000 per cubic millimeter. When the base-line hematocrit was lowered, the serum porphyrin levels increased; the base-line hematocrit was subsequently kept at 39 percent or higher.At puberty, hemoglobin in children increases to the levels in adults; these levels are higher in males than in females, probably as a result of increased androgen production. Androgen-responsive promoters have recently been identified, and they may be linked, at least in hemophilia B Leyden, to changes at puberty5. In our patient, puberty was associated with a relapse of congenital erythropoietic porphyria. We attributed his relapse to increased erythropoiesis and successfully suppressed this increase by administering hydroxyurea. The transfusion requirement, however, could not be reduced; if the hematocrit was lowered to less than 39 percent, the serum porphyrin concentrations rose to levels that produced photosensitivity.
In patients with sickle cell disease or β-thalassemia who undergo transfusion, a goal of hypertransfusion is to suppress endogenous erythropoiesis. Our experience with the use of hydroxyurea in a patient with congenital erythropoietic porphyria suggests that the addition of hydroxyurea in patients with these other conditions may similarly suppress erythropoiesis and possibly reduce transfusion requirements.
5 ReferencesLudovico Guarini, M.D.
Sergio Piomelli, M.D.
Columbia University, New York, NY 10032Maureen B. Poh-Fitzpatrick, M.D.
New York Medical College, Valhalla, NY 105951
Nordmann Y ,Deybach JC . Congenital erythropoietic porphyria. Semin Liver Dis 1982;2:154-163
CrossRef | Medline2
Haining RG ,Cowger ML ,Labbe RF ,Finch CA . Congenital erythropoietic porphyria. II. The effects of induced polycythemia. Blood 1970;36:297-309
Web of Science | Medline3
Piomelli S ,Poh-Fitzpatrick MB ,Seaman C ,Skolnick LM ,Berdon WE . Complete suppression of the symptoms of congenital erythropoietic porphyria by long-term treatment with high-level transfusions. N Engl J Med 1986;314:1029-1031
Full Text | Web of Science | Medline4
West WO . Hydroxyurea in the treatment of polycythemia vera: a prospective study of 100 patients over a 20-year period. South Med J 1987;80:323-327
CrossRef | Web of Science | Medline5
Crossley M ,Ludwig M ,Stowell KM ,De Vos P ,Olek K ,Brownlee GG . Recovery from Hemophilia B Leyden: an androgen-responsive element in the factor IX promoter. Science 1992;257:377-379
CrossRef | Web of Science | Medline
- Citing Articles (20)
Citing Articles
1
Jose M. Mascaro, Henry W. Lim. 2011. Porphyrias. , 107.1-107.18.
CrossRef2
Arola Fortian, David Castaño, Esperanza Gonzalez, Ana Laín, Juan M. Falcon-Perez, Oscar Millet. 2011. Structural, thermodynamic, and mechanistical studies in uroporphyrinogen III synthase:Molecular basis of congenital erythropoietic porphyria. , 43-74.
CrossRef3
I. Lebreuilly-Sohyer, A. Morice, A. Acher, A. Dompmartin, C. Clement, H. de Verneuil, C. Ged, D. Leroy, L. Verneuil. (2010) Porphyrie érythropoïétique congénitale traitée par allogreffe de cellules souches hématopoïétiques. Annales de Dermatologie et de Vénéréologie 137:10, 635-639
CrossRef4
R. P. E. Sarkany, S. M. Breathnach, A. A. M. Morris, K. Weismann, P. D. Flynn. 2010. Metabolic and Nutritional Disorders. , 1-103.
CrossRef5
D. F. Bishop, X. Schneider-Yin, S. Clavero, H.-W. Yoo, E. I. Minder, R. J. Desnick. (2010) Congenital erythropoietic porphyria: a novel uroporphyrinogen III synthase branchpoint mutation reveals underlying wild-type alternatively spliced transcripts. Blood 115:5, 1062-1069
CrossRef6
S.M. Taibjee, O.E. Stevenson, A. Abdullah, C.Y. Tan, P. Darbyshire, C. Moss, H. Goodyear, A. Heagerty, S. Whatley, M.N. Badminton. (2007) Allogeneic bone marrow transplantation in a 7-year-old girl with congenital erythropoietic porphyria: a treatment dilemma. British Journal of Dermatology 156:3, 567-571
CrossRef7
Shigeru Sassa. (2006) Modern diagnosis and management of the porphyrias. British Journal of Haematology 135:3, 281-292
CrossRef8
David F. Bishop, Annika Johansson, Robert Phelps, Amr A. Shady, Maria C.M. Ramirez, Makiko Yasuda, Andres Caro, Robert J. Desnick. (2006) Uroporphyrinogen III Synthase Knock-In Mice Have the Human Congenital Erythropoietic Porphyria Phenotype, Including the Characteristic Light-Induced Cutaneous Lesions. The American Journal of Human Genetics 78:4, 645-658
CrossRef9
Deepika Pandhi, Mansi Suman, Neeta Khurana, B. S. N. Reddy. (2003) Congenital Erythropoietic Porphyria Complicated by Squamous Cell Carcinoma. Pediatric Dermatology 20:6, 498-501
CrossRef10
Robert J. Dsnick, Kenneth H. Astrin. (2002) Congenital erythropoietic porphyria: advances in pathogenesis and treatment. British Journal of Haematology 117:4, 779-795
CrossRef11
Nabil Saba, Thomas Flaig. (2002) Bone Marrow Transplantation for Nonmalignant Diseases. Journal of Hematotherapy <html_ent glyph="@amp;" ascii="&"/> Stem Cell Research 11:2, 377-387
CrossRef12
Herbert L. Bonkovsky, Graham F. Barnard. (2000) The porphyrias. Current Treatment Options in Gastroenterology 3:6, 487-499
CrossRef13
H LIM, J COHEN. (1999) The cutaneous porphyrias. Seminars in Cutaneous Medicine and Surgery 18:4, 285-292
CrossRef14
Herrera Saval, Moruno Tirado. (1999) Congenital erythropoietic porphyria affecting two brothers. British Journal of Dermatology 141:3, 547-550
CrossRef15
Hes, Slootweg, van Vroonhoven, Hene, Feldberg, Zewald, Ploos van Amstel, Hoppener, Pearson, Lips. (1999) Management of renal cell carcinoma in von Hippel-Lindau disease. European Journal of Clinical Investigation 29:1, 68-75
CrossRef16
J. M. Mascaro. (1998) Management of the erythropoietic porphyrias. Photodermatology, Photoimmunology & Photomedicine 14:2, 44-45
CrossRef17
M Mathews-Roth. (1998) Treatment of the Cutaneous Porphyrias. Clinics in Dermatology 16:2, 295-298
CrossRef18
Hartmut P H Neumann, Berton Zbar. (1997) Renal cysts, renal cancer and von Hippel-Lindau disease. Kidney International 51:1, 16-26
CrossRef19
Henry W. Lim, Gillian M. Murphy. (1996) The porphyrias. Clinics in Dermatology 14:4, 375-387
CrossRef20
Hartmut P.H. Neumann, Cornells J.M. Lips, Y. Edward Hsia, Berton Zbar. (1995) Von Hippel-Lindau Syndrome. Brain Pathology 5:2, 181-193
CrossRef
