Correspondence

Epoetin for Severe Anemia in Hepatoerythropoietic Porphyria

N Engl J Med 2000; 342:1294-1295April 27, 2000

Article

To the Editor:

Hepatoerythropoietic porphyria is a rare autosomal recessive disorder of heme biosynthesis caused by a deficiency of uroporphyrinogen decarboxylase. Excessive accumulation of photoactive porphyrins in the skin, bone marrow, and peripheral blood results in photodermatitis, secondary skin infections, and “intractable” anemia.1 We report the successful treatment of life-threatening anemia with recombinant human erythropoietin (epoetin) in a patient with late-onset hepatoerythropoietic porphyria.

A 68-year-old white man (Karnofsky score, 20)2 with a 36-year history of porphyria and anemia was admitted for severe heart failure (left ventricular ejection fraction, 30 percent). Disfiguring scarring with inflamed erosions was present on sites exposed to the sun, particularly the face, scalp, and hands. Laboratory values included the following: hemoglobin, 5.8 g per deciliter; mean corpuscular volume, 54 μm³; ratio of reticulocytes to red cells, 5:1000; serum erythropoietin, 38 mU per milliliter (normal range, 5 to 27); ferritin, 46 μg per liter (normal value, >15); serum iron, 2.7 μmol per liter (normal range, 7.2 to 21.5); transferrin saturation, 3 percent (normal value, >15); plasma fibrinogen, 445 mg per deciliter (normal range, 170 to 400); C-reactive protein, 74 mg per liter (normal value, <5); haptoglobin, 3.1 g per liter (normal range, 0.5 to 2.2); and gamma globulin, 1.66 g per deciliter (normal range, 0.6 to 1.5). Porphyrin analysis revealed extremely elevated levels of urinary uroporphyrin I and III, 7-carboxyl porphyrins, fecal coproporphyrins and isoporphyrins, and erythrocytic protoporphyrin. Studies of enzyme activity revealed a profound deficiency of uroporphyrinogen decarboxylase in erythrocytes (16 percent of normal).

Initially, two blood transfusions were given. A 10-day trial of intravenous iron failed to increase the hemoglobin level and reticulocyte count. Endogenous erythropoietin levels were too low for the degree of anemia, as is typical in patients with chronic disorders.3 We thus commenced therapy with subcutaneous epoetin (Figure 1Figure 1Hemoglobin Levels and Reticulocyte Counts during Epoetin Therapy in a 68-Year-Old Man with Hepatoerythropoietic Porphyria.). Although total urinary porphyrins increased by a factor of almost six after therapy (from 1621 to 9480 μg per liter; normal value, <150), the patient's acute skin lesions improved. Partial correction of the anemia in response to epoetin resulted in an improved left ventricular ejection fraction (50 percent) and Karnofsky score (60 percent). The patient required no further hospitalization during 22 months of follow-up while receiving epoetin.

We conclude that anemia in patients with hepatoerythropoietic porphyria can no longer be considered intractable, since treatment with epoetin corrected severe anemia in our patient. Endogenous levels of erythropoietin were inadequately increased, and pharmacologic doses of epoetin helped to overcome this relative deficiency. In contrast to its effect in a patient with porphyria cutanea tarda on long-term hemodialysis,4 epoetin treatment increased the total porphyrin levels in our patient, presumably by stimulating heme synthesis, but was nevertheless associated with an overall clinical benefit.

Jörg H. Horina, M.D.
Peter Wolf, M.D.
Karl-Franzens University, A-8036 Graz, Austria

4 References

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   Full Text | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   D.K.B. Armstrong, P.C. Sharpe, C.R. Chambers, S.D. Whatley, A.G. Roberts, G.H. Elder. (2004) Hepatoerythropoietic porphyria: a missense mutation in the UROD gene is associated with mild disease and an unusual porphyrin excretion pattern. British Journal of Dermatology 151:4, 920-923
   CrossRef

2. 2

   Andrea S Winkler, Timothy J Peters, Joanne T Marsden, Allan C Deacon, Georgina Chandler, Iain C Macdougall. (2003) Erythropoietin treatment in the neuropsychiatric porphyrias. Clinica Chimica Acta 338:1-2, 61-66
   CrossRef