Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder characterized by photosensitivity and by hematologic abnormalities in affected individuals. CEP is caused by mutations in the uroporphyrinogen synthase (UROS) gene. In three reported cases, CEP has been associated with a specific X-linked GATA1 mutation. Disease-causing mutations in either gene result in absent or markedly reduced UROS enzymatic activity. This in turn leads to the accumulation of the non-physiologic and photoreactive porphyrinogens, uroporphyrinogen I and coproporphyrinogen I, which damage erythrocytes and elicit a phototoxic reaction upon light exposure. The clinical spectrum of CEP depends on the level of residual UROS activity, which is determined by the underlying pathogenic loss-of-function UROS mutations. Disease severity ranges from non-immune hydrops fetalis in utero to late-onset disease with only mild cutaneous involvement. The clinical characteristics of CEP include exquisite photosensitivity to visible light resulting in bullous vesicular lesions which, when infected lead to progressive photomutilation of sun-exposed areas such as the face and hands. In addition, patients have erythrodontia (brownish discoloration of teeth) and can develop corneal scarring. Chronic transfusion-dependent hemolytic anemia is common and leads to bone marrow hyperplasia, which further increases porphyrin production. Management of CEP consists of strict avoidance of exposure to visible light with sun-protective clothing, sunglasses, and car and home window filters. Adequate care of ruptured vesicles and use of topical antibiotics is indicated to prevent superinfections and osteolysis. In patients with symptomatic hemolytic anemia, frequent erythrocyte cell transfusions may be necessary to suppress hematopoiesis and decrease marrow production of the phototoxic porphyrins. In severe transfection-dependent cases, bone marrow or hematopoietic stem cell transplantation has been performed, which is curative. Therapeutic approaches including gene therapy, proteasome inhibition, and pharmacologic chaperones are under investigation.

中文翻译：

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先天性红细胞生成性卟啉症：最新进展。

先天性红细胞生成性卟啉症（CEP）是一种罕见的常染色体隐性遗传疾病，其特征在于受感染者的光敏性和血液学异常。CEP是由尿卟啉原合酶（UROS）基因突变引起的。在三例报道的病例中，CEP与特定的X连锁GATA1突变相关。任一基因中的致病突变导致UROS酶活性缺失或显着降低。这继而导致非生理性和光反应性卟啉原，尿卟啉原I和协同原卟啉原I的积累，它们会损害红细胞并在光照下引起光毒性反应。CEP的临床范围取决于残留的UROS活性水平，该水平由潜在的致病性功能丧失UROS突变决定。疾病的严重程度从子宫内的非免疫性胎儿水肿到仅轻度皮肤受累的迟发性疾病。CEP的临床特征包括对可见光的极高的光敏性，导致大疱性囊泡病变；当感染时，会导致逐渐暴露于日光照射的区域（如脸部和手部）的光致残害。此外，患者患有红斑牙病（牙齿呈褐色变色），并可能发展为角膜瘢痕。慢性输血依赖性溶血性贫血很常见，并导致骨髓增生，进一步增加了卟啉的产生。CEP的管理包括严格避免使用防晒衣，太阳镜以及汽车和家用窗户滤光片暴露在可见光下。指出要充分照顾破裂的囊泡并使用局部抗生素，以防止过度感染和骨溶解。在有症状的溶血性贫血患者中，可能需要频繁输注红细胞以抑制造血作用并减少骨髓中光毒性卟啉的产生。在严重的转染依赖性病例中，已经进行了骨髓或造血干细胞移植，这是治愈性的。目前正在研究包括基因治疗，蛋白酶体抑制和药理伴侣蛋白在内的治疗方法。已经进行了骨髓或造血干细胞移植，这是治愈性的。目前正在研究包括基因治疗，蛋白酶体抑制和药理伴侣蛋白在内的治疗方法。已经进行了骨髓或造血干细胞移植，这是治愈性的。目前正在研究包括基因治疗，蛋白酶体抑制和药理伴侣蛋白在内的治疗方法。