Tezcan I, Xu W, Gurgey A, Tuncer M, Cetin M, Oner C, Yetgin S, Ersoy F, Aizencang G, Astrin K H, Desnick R J
Department of Pediatric Immunology and Hematology, Hacettepe University, Ankara, Turkey.
Blood. 1998 Dec 1;92(11):4053-8.
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.
在一名患有先天性红细胞生成性卟啉病（CEP）的18个月大严重受影响、依赖输血的女性患者中，显示了同种异体骨髓移植（BMT）的长期生化和临床疗效。CEP是一种常染色体隐性遗传性血红素生物合成先天性缺陷疾病，由尿卟啉原III合成酶（URO合成酶）基因突变引起。骨髓移植三年后，受者血红蛋白正常，尿卟啉排泄显著减少，且在无限制暴露于阳光下时无皮肤病变。该患者为新型URO合成酶错义突变G188R的纯合子，该突变在大肠杆菌中表达的活性低于正常平均活性的5%，这与她对输血的依赖性一致。由于CEP的临床严重程度差异很大，从非免疫性胎儿水肿到仅伴有皮肤病变的较轻、较晚发病形式，因此强调对新诊断婴儿进行基因分型以选择严重受影响患者进行BMT的重要性。此外，该患者骨髓移植的长期疗效为未来对严重受影响的CEP患者进行造血干细胞基因治疗提供了理论依据。
