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Congenital erythropoietic porphyria successfully treated by allogeneic bone marrow transplantation
1Department of Pediatric Immunology and Hematology, Hacettepe University, Ankara, Turkey.
Insights
Allogeneic bone marrow transplantation (BMT) offers long-term biochemical and clinical benefits for severe congenital erythropoietic porphyria (CEP). This treatment normalized hemoglobin and reduced porphyrin excretion, improving the patient's quality of life.
Area of Science:
- Hematology
- Genetics
- Biochemistry
Background:
- Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder of heme biosynthesis.
- Mutations in the uroporphyrinogen III synthase (URO-synthase) gene cause CEP, leading to severe symptoms.
- Clinical severity of CEP varies widely, impacting treatment decisions.
Observation:
- A severely affected, transfusion-dependent 18-month-old female with CEP was treated with allogeneic bone marrow transplantation (BMT).
- The patient presented with a novel G188R URO-synthase mutation, expressing <5% normal activity.
- Three years post-BMT, the patient exhibited normal hemoglobin, reduced porphyrin excretion, and no skin lesions.
Findings:
- Allogeneic BMT demonstrated long-term biochemical and clinical effectiveness in a severely affected CEP patient.
- Successful BMT normalized key hematological markers and significantly reduced porphyrin levels.
- The patient tolerated sunlight exposure without cutaneous manifestations post-transplantation.
Implications:
- Genotyping infants with CEP is crucial for identifying severely affected individuals who may benefit from BMT.
- BMT offers a viable therapeutic option for severe congenital erythropoietic porphyria.
- This case supports future research into hematopoietic stem cell gene therapy for CEP.
Abstract:
The long-term biochemical and clinical effectiveness of allogenic bone marrow transplantation (BMT) was shown in a severely affected, transfusion-dependent 18-month-old female with congenital erythropoietic porphyria (CEP), an autosomal recessive inborn error of heme biosynthesis resulting from mutations in the uroporphyrinogen III synthase (URO-synthase) gene. Three years post-BMT, the recipient had normal hemoglobin, markedly reduced urinary porphyrin excretion, and no cutaneous lesions with unlimited exposure to sunlight. The patient was homoallelic for a novel URO-synthase missense mutation, G188R, that expressed less than 5% of mean normal activity in Escherichia coli, consistent with her transfusion dependency. Because the clinical severity of CEP is highly variable, ranging from nonimmune hydrops fetalis to milder, later onset forms with only cutaneous lesions, the importance of genotyping newly diagnosed infants to select severely affected patients for BMT is emphasized. In addition, the long-term effectiveness of BMT in this patient provides the rationale for future hematopoietic stem cell gene therapy in severely affected patients with CEP.