Inducing iron deficiency improves erythropoiesis and photosensitivity in congenital erythropoietic porphyria
Inducing iron deficiency improves erythropoiesis and photosensitivity in congenital erythropoietic porphyria
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DOI：
10.1182/blood-2014-07-584664
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发表时间：
2015-07-09
期刊：
影响因子：
20.3
通讯作者：
Abkowitz, Janis L.
中科院分区：
文献类型：
--
作者：
Egan, Daniel N.;Yang, Zhantao;Abkowitz, Janis L.
先天性红细胞生成性卟啉症（CEP）是一种常染色体隐性遗传的血红素合成障碍，其特征是尿卟啉原III合酶活性降低和非生理性异构体I卟啉代谢产物的积累，导致无效的红细胞生成和破坏性的皮肤光敏性。疾病的管理主要包括支持性措施。5-氨基乙酰丙酸合酶2（ALAS 2）的活性增加已显示不利地改变疾病表型。在此，我们提出了一个病人与CEP谁表现出显着改善疾病的表现，在设置缺铁。假设铁限制通过降低ALAS 2活性和随后的卟啉产生来改善她的症状，我们用地拉罗司的标签外使用来治疗患者以维持铁缺乏，结果是成功的。我们通过骨髓培养研究证实了她的生理反应。
Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder of heme synthesis characterized by reduced activity of uroporphyrinogen III synthase and the accumulation of nonphysiologic isomer I porphyrin metabolites, resulting in ineffective erythropoiesis and devastating skin photosensitivity. Management of the disease primarily consists of supportive measures. Increased activity of 5-aminolevulinate synthase 2 (ALAS2) has been shown to adversely modify the disease phenotype. Herein, we present a patient with CEP who demonstrated a remarkable improvement in disease manifestations in the setting of iron deficiency. Hypothesizing that iron restriction improved her symptoms by decreasing ALAS2 activity and subsequent porphyrin production, we treated the patient with off-label use of deferasirox to maintain iron deficiency, with successful results. We confirmed the physiology of her response with marrow culture studies.