Erythropoietic Protoporphyria (EPP) and X-linked Protoporphyria (XLP) are rare, genetic photodermatoses resulting from defects in enzymes of the heme-biosynthetic pathway. EPP results from the partial deficiency of ferrochelatase, and XLP results from gain-of-function mutations in erythroid specific ALAS2. Both disorders result in the accumulation of erythrocyte protoporphyrin, which is released in the plasma and taken up by the liver and vascular endothelium. The accumulated protoporphyrin is activated by sunlight exposure, generating singlet oxygen radical reactions leading to tissue damage and excruciating pain. About 2-5% of patients develop clinically significant liver dysfunction due to protoporphyrin deposition in bile and/or hepatocytes which can advance to cholestatic liver failure requiring transplantation. Clinically these patients present with acute, severe, non-blistering phototoxicity within minutes of sun-exposure. Anemia is seen in about 47% of patients and about 27% of patients will develop abnormal serum aminotransferases. The diagnosis of EPP and XLP is made by detection of markedly increased erythrocyte protoporphyrin levels with a predominance of metal-free protoporphyrin. Genetic testing by sequencing the FECH or ALAS2 gene confirms the diagnosis. Treatment is limited to sun-protection and there are no currently available FDA-approved therapies for these disorders. Afamelanotide, a synthetic analogue of α-melanocyte stimulating hormone was found to increase pain-free sun exposure and improve quality of life in adults with EPP. It has been approved for use in the European Union since 2014 and is not available in the U.S. In addition to the development of effective therapeutics, future studies are needed to establish the role of iron and the risks related to the development of hepatopathy in these patients.

中文翻译：

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红细胞原卟啉和X连锁原卟啉：病理生理学，遗传学，临床表现和管理。

红血球原核生物（EPP）和X连锁原核生物（XLP）是罕见的遗传性光皮病，是由血红素生物合成途径的酶缺陷引起的。EPP是由铁螯合酶的部分缺乏引起的，XLP是由红系特异性ALAS2的功能获得性突变引起的。两种疾病都会导致红血球原卟啉积聚，并在血浆中释放并被肝脏和血管内皮吸收。积累的原卟啉被阳光照射激活，产生单线态氧自由基反应，从而导致组织损伤和疼痛。由于原卟啉在胆汁和/或肝细胞中的沉积，约有2-5％的患者发展出临床上明显的肝功能不全，这可能会发展为需要移植的胆汁淤积性肝衰竭。临床上，这些患者在暴露于阳光下的几分钟内表现出急性，严重，非起泡的光毒性。在约47％的患者中发现贫血，约27％的患者会发展出异常的血清氨基转移酶。EPP和XLP的诊断是通过检测以无金属原卟啉为主的红细胞原卟啉水平显着增加来进行的。通过对FECH或ALAS2基因进行测序的遗传测试证实了诊断。治疗仅限于防晒，目前尚无FDA批准的针对这些疾病的疗法。人们发现，α-黑素细胞刺激激素的合成类似物Afamelanotide可以增加EPP成年人的无痛日光照射并改善生活质量。自2014年以来，它已获准在欧盟使用，在美国则不可用。