Very Early Diagnosis and Management of Congenital Erythropoietic Porphyria

Abstract

Congenital erythropoietic porphyria (CEP), a rare form of porphyria, is caused by a defect in the heme biosynthesis pathway of the enzyme uroporphyrinogen III synthase (UROS). Uroporphyrinogen III synthase deficiency leads to an accumulation of nonphysiological porphyrins in bone marrow, red blood cells, skin, bones, teeth, and spleen. Consequently, the exposure to sunlight causes severe photosensitivity, long-term intravascular hemolysis, and eventually, irreversible mutilating deformities. Several supportive therapies such as strict sun avoidance, physical sunblocks, red blood cells transfusions, hydroxyurea, and splenectomy are commonly used in the management of CEP. Currently, the only available curative treatment of CEP is hematopoietic stem cell transplantation (HSCT). In this article, we present a young girl in which precocious genetic testing enabled early diagnosis and allowed curative treatment with HSCT for CEP at the age of 3 months of age, that is, the youngest reported case thus far.

Successful treatment of congenital erythropoietic porphyria using matched unrelated hematopoietic stem cell transplantation in an adult: A case report

“…Indeed, UROIIIS deficiency is still present in non‐erythroid tissues (for example liver cells) and can lead to a persistent accumulation of porphyrins despite full replacement of erythroid tissues with HSCT as shown by the erythrocyte porphyrins chromatography. Other studies have described a similar situation 4,12 . As reported here, plasma porphyrin levels remain below a clinically relevant threshold and did not to impair major clinical improvement of skin lesions.…”

“…This patient unfortunately died from cytomegalovirus infection after transplant but an encouraging haematologic response was documented. Since then, multiple other paediatric cases have been published showing the efficacy of ASCT to cure CEP 2,4,6–15 . Interestingly, a tandem sequential liver transplant and Allo‐SCT from the same haploidentical donor has been reported in a child with CEP, this strategy allowing for discontinuation of immune suppression 13 .…”

“…Since then, multiple other paediatric cases have been published showing the efficacy of ASCT to cure CEP. 2 , 4 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 Interestingly, a tandem sequential liver transplant and Allo‐SCT from the same haploidentical donor has been reported in a child with CEP, this strategy allowing for discontinuation of immune suppression. 13 This highlights the potential role of Allo‐SCT in patients needing solid transplant to avoid prolonged immunosuppression, risk of infection, or rejection by inducing tolerance of the transplanted solid organ.…”

“…Symptomatic treatments are ineffective in this serious disease and allogeneic stem cell transplantation (Allo‐SCT) remains the only curative procedure for those eligible. Successful experiences with Allo‐SCT have been reported in children 3–13 . However, at our knowledge, no such data exist in adults with CEP.…”

“…Successful experiences with Allo-SCT have been reported in children. [3][4][5][6][7][8][9][10][11][12][13] However, at our knowledge, no such data exist in adults with CEP.…”