Clinical characteristics and treatment exploration of patients with erythropoietic protoporphyria: a literature review and single-center case analysis_West China Medical Journal

Authors：

LIU Ruihong ¹ , KANG Ninglin ² , HU Yuanxiang ³ , WU Jiahong ³ ,  ZHANG Songyun ^1,4 ,  WANG Ying ⁵

1. Department of Endocrinology, Metabolism and Rare Diseases, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P. R. China;
2. Department of Endocrinology, Hebei Hospital of Traditional Chinese Medicine, Shijiazhuang, Hebei 050000, P. R. China;
3. Department of Geriatrics, the First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, P. R. China;
4. Key Laboratory of Rare Diseases of Hebei Province, Shijiazhuang, Hebei 050000, P. R. China;
5. Department of Hematology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P. R. China;

Corresponding?author：

ZHANG Songyun, Email: zsyinsjz@hebmu.edu.cn; WANG Ying, Email: wangying730@126.com

Keywords：

Erythropoietic protoporphyria; genetic characteristics; liver injury; therapeutic phlebotomy

DOI：

10.7507/1002-0179.202512132

Video：

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Objective To summarize the clinical and genetic characteristics of patients with erythropoietic protoporphyria (EPP) and explore treatment strategies for this disease. Methods We systematically searched Chinese and English databases (PubMed, China National Knowledge Infrastructure, Wanfang, VIP database, and China Biomedical Literature Service System) for case reports on Chinese (including overseas Chinese) EPP patients published up to November 2025. Data from 7 genetically confirmed patients diagnosed at the Second Hospital of Hebei Medical University were retrospectively analyzed. A descriptive comparison was conducted between the aggregated data of Chinese patients and published large-scale foreign studies with clear population representativeness. Results A total of 46 EPP patients were included, with 44 from China and 2 from Singapore, comprising 40 males (87.0%) and 6 females (13.0%). The median age at onset was 4 years, the median age at diagnosis was 26 years, and the median diagnostic delay was 18.5 years. Patients who initially presented with cutaneous manifestations (n=14) had a significantly shorter diagnostic delay than those presenting with hepatic or other manifestations (n=32) (7 vs. 24.5 years, Z=–2.160, P=0.031). Liver function impairment was present in 92.9% (39/42) of patients. Genetically, 50.0% (23/46) of patients exhibited compound heterozygous pathogenic variants in the FECH gene, and 78.3% (36/46) carried the c.315-48T>C variant. Strict photoprotection served as the cornerstone of management. Patients with concomitant liver disease received additional treatments such as ursodeoxycholic acid, glucocorticoids, plasma exchange, or liver transplantation. Notably, two patients from the Second Hospital of Hebei Medical University showed significant clinical improvement following therapeutic phlebotomy. There were differences in the clinical and genetic characteristics of EPP patients between Chinese and other ethnic groups. Conclusions Chinese (including Singaporean Chinese) EPP patients are characterized by male predominance, a high prevalence of the c.315-48T>C variant, frequent liver injury, and significant diagnostic delay. EPP should be suspected in cases of unexplained photosensitivity accompanied by hepatic dysfunction. Therapeutic phlebotomy may represent a valuable exploratory option for EPP patients.

Citation： LIU Ruihong, KANG Ninglin, HU Yuanxiang, WU Jiahong, ZHANG Songyun, WANG Ying. Clinical characteristics and treatment exploration of patients with erythropoietic protoporphyria: a literature review and single-center case analysis. West China Medical Journal, 2026, 41(1): 24-32. doi: 10.7507/1002-0179.202512132 Copy

1.	Chiara M, Primon I, Tarantini L, et al. Targeted resequencing of FECH locus reveals that a novel deep intronic pathogenic variant and eQTLs may cause erythropoietic protoporphyria (EPP) through a methylation-dependent mechanism. Genet Med, 2020, 22(1): 35-43.
2.	Wu CK, Dailey HA, Rose JP, et al. The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis. Nat Struct Biol, 2001, 8(2): 156-160.
3.	Phillips JD. Heme biosynthesis and the porphyrias. Mol Genet Metab, 2019, 128(3): 164-177.
4.	Long ZB, Wang YW, Yang C, et al. Identification of FECH gene multiple variations in two Chinese patients with erythropoietic protoporphyria and a review. J Zhejiang Univ Sci B, 2016, 17(10): 813-820.
5.	Lala SM, Naik H, Balwani M. Diagnostic delay in erythropoietic protoporphyria. J Pediatr, 2018, 202: 320-323.e2.
6.	Coffey A, Leung DH, Quintanilla NM. Erythropoietic protoporphyria: initial diagnosis with cholestatic liver disease. Pediatrics, 2018, 141(Suppl 5): S445-S450.
7.	Zhou SN, Xiao SX, Peng ZH, et al. A novel mutation of the FECH gene in a Chinese family with erythropoietic protoporphyria. J Dermatol Sci, 2007, 48(2): 145-147.
8.	Zhang F, Lu L, Qian X, et al. Liver transplantation for erythropoietic protoporphyria with hepatic failure: a case report. Transplant Proc, 2008, 40(5): 1774-1776.
9.	Kong XF, Ye J, Gao DY, et al. Identification of a ferrochelatase mutation in a Chinese family with erythropoietic protoporphyria. J Hepatol, 2008, 48(2): 375-379.
10.	Lau KC, Lam CW, Fong B, et al. DNA-based diagnosis of erythropoietic protoporphyria in two families and the frequency of a low-expression FECH allele in a Chinese population. Clin Chim Acta, 2009, 400(1/2): 132-134.
11.	Ma J, Xiao S, An J, et al. A novel splicing mutation and haplotype analysis of the FECH gene in a Chinese family with erythropoietic protoporphyria. J Eur Acad Dermatol Venereol, 2010, 24(6): 726-729.
12.	Chuah SY, Tee SI, Pramono ZA, et al. Genetic study in a Singaporean patient with erythropoietic protoporphyria. Photodermatol Photoimmunol Photomed, 2012, 28(5): 269-271.
13.	彭瑩, 李浩賢, 劉靜, 等. 一例紅細胞生成性卟啉病報道//第十二次全國醫學遺傳學學術會議論文匯編. 鄭州: 中華醫學會醫學遺傳學分會, 中國遺傳學會人類和醫學遺傳學委員會, 2014: 105-106.
14.	Cheung CY, Tam S, Lam CW, et al. Allogeneic haematopoietic stem cell transplantation for erythropoietic protoporphyria: a cautionary note. Blood Cells Mol Dis, 2015, 54(3): 266-267.
15.	Alagappan U, Pramono ZA, Chong WS. Ferrochelatase gene mutation in Singapore and a novel frame-shift mutation in an Asian boy with erythropoietic protoporphyria. Int J Dermatol, 2017, 56(3): 272-276.
16.	李曉青, 師杰, 賴雅敏, 等. 4 例以黃疸為主要表現的紅細胞生成性原卟啉病臨床、病理及遺傳學分析. 臨床肝膽病雜志, 2017, 33(7): 1332-1335.
17.	馮靈美, 曹盼, 喬秀敏, 等. 以腹痛合并肝損傷為主要表現的紅細胞生成性原卟啉病. 中華消化雜志, 2017, 37(2): 123-125.
18.	曹麗麗, 董漪, 儲芳, 等. 以肝衰竭為主要表現的紅細胞生成性原卟啉病 1 例報告. 臨床肝膽病雜志, 2018, 34(9): 1975-1978.
19.	李東良, 方堅, 張志強, 等. 以肝硬化食管胃靜脈破裂出血就診的紅細胞生成性原卟啉病. 中華消化雜志, 2018, 38(4): 275-278.
20.	Liu HM, Deng GH, Mao Q, et al. Diagnosis of erythropoietic protoporphyria with severe liver injury: a case report. World J Gastroenterol, 2019, 25(7): 880-887.
21.	Jiang Z, Jiang X, Chen M. Severe aplastic anemia in a patient with erythropoietic protoporphyria successfully treated by avatrombopag. Ann Hematol, 2022, 101(6): 1361-1363.
22.	馬春苗, 于辛酉, 陸彪, 等. 兒童紅細胞生成性原卟啉病多器官功能衰竭一例并文獻復習. 中國全科醫學, 2021, 24(32): 4160-4163.
23.	馬莉, 李洪杰, 段雪飛. 以肝功能異常為主要表現的紅細胞生成性原卟啉病 1 例. 中國肝臟病雜志(電子版), 2021, 13(3): 68-72.
24.	楊秋萍, 李小紅, 聞娟, 等. 一例紅細胞生成性原卟啉病臨床分析及 FECH 基因檢測. 中國麻風皮膚病雜志, 2021, 37(4): 193-197.
25.	李會, 李晨, 劉曉燕, 等. 以肝硬化合并急性腹痛為表現的紅細胞生成性原卟啉病 1 例. 傳染病信息, 2021, 34(3): 282-286.
26.	孫鈺楨, 張江安, 于建斌, 等. 紅細胞生成性原卟啉病一家系基因突變分析. 中國皮膚性病學雜志, 2021, 35(4): 393-396, 412.
27.	Zhao C, Guan JX, Hui DY, et al. Liver involvement in patients with erythropoietic protoporphyria: retrospective analysis of clinicopathological features of 5 cases. Ann Diagn Pathol, 2022, 56: 151859.
28.	Huang HQ, Cai LQ, Li XH, et al. Diagnosis and treatment of icteric hepatitis caused by erythropoietic protoporphyria: a case report. Liver Res, 2022, 6(2): 116-120.
29.	李清清, 陳小燕, 王紅, 等. 成年女性紅細胞生成性原卟啉病合并甲狀腺功能亢進癥和肝功能障礙 1 例. 中南大學學報(醫學版), 2023, 48(11): 1768-1774.
30.	Tan Q, Yang HF, Lan LF. Two novel mutations in FECH in a patient with erythropoietic protoporphyria: a case report. Int J Dermatol Venereol, 2023, 6(2): 112-114.
31.	謝瑩, 張源凈, 杭小鋒, 等. 以腹痛、黃疸、肝脾腫大為表現的紅細胞生成性原卟啉病 1 例. 肝臟, 2023, 28(2): 245-246.
32.	Zeng T, Chen SR, Liu HQ, et al. Successful treatment of severe hepatic impairment in erythropoietic protoporphyria: a case report and review of literature. World J Hepatol, 2024, 16(6): 966-972.
33.	Wu SH, Xiao T, Zhao D, et al. Case report: Xeroderma pigmentosum Group A with erythropoietic protoporphyria in a young Chinese patient. Front Endocrinol (Lausanne), 2024, 15: 1418254.
34.	Wu X, Zhou X, Zhao S, et al. Treatment strategy for erythropoietic protoporphyria accompanied by severe abdominal pain and liver injury. Port Hypertens Cirrhos, 2024, 3: 36-38.
35.	吳振東, 周國強, 向燕, 等. 以肝硬化為主要表現的紅細胞生成性原卟啉病 1 例報告. 臨床肝膽病雜志, 2024, 40(3): 581-584.
36.	Xiong HL, He S, Yang ZX, et al. Erythropoietic protoporphyria linked to intricate double heterozygous mutations in the FECH gene: a case report and literature review. Orphanet J Rare Dis, 2025, 20(1): 333.
37.	Yang TT, Chen CX, Li CM, et al. Challenges in the pathological diagnosis of erythropoietic protoporphyria: a case report. Front Med (Lausanne), 2025, 12: 1664961.
38.	Zhang YJ, Huang SP, Shang ZY, et al. Recurrent liver dysfunction in erythropoietic protoporphyria: a case with compound heterozygous FECH mutations. J Dig Dis, 2025, 26(5/6): 260-263.
39.	Mizawa M, Makino T, Nakano H, et al. Erythropoietic protoporphyria in a Japanese population. Acta Derm Venereol, 2019, 99(7): 634-639.
40.	Holme SA, Anstey AV, Finlay AY, et al. Erythropoietic protoporphyria in the U.K. : clinical features and effect on quality of life. Br J Dermatol, 2006, 155(3): 574-581.
41.	Wahlin S, Floderus Y, St?l P, et al. Erythropoietic protoporphyria in Sweden: demographic, clinical, biochemical and genetic characteristics. J Intern Med, 2011, 269(3): 278-288.
42.	Balwani M, Doheny D, Bishop DF, et al. Loss-of-function ferrochelatase and gain-of-function erythroid-specific 5-aminolevulinate synthase mutations causing erythropoietic protoporphyria and x-linked protoporphyria in North American patients reveal novel mutations and a high prevalence of X-linked protoporphyria. Mol Med, 2013, 19(1): 26-35.
43.	Heerfordt IM, Lerche CM, Wulf HC. Trends in erythrocyte protoporphyrin IX concentration by age, sex and season among patients with erythropoietic protoporphyria-20 years of follow-up. Photodiagnosis Photodyn Ther, 2020, 32: 101928.
44.	Barman-Aks?zen J, Minder EI, Schubiger C, et al. In ferrochelatase-deficient protoporphyria patients, ALAS2 expression is enhanced and erythrocytic protoporphyrin concentration correlates with iron availability. Blood Cells Mol Dis, 2015, 54(1): 71-77.
45.	B?hm M, Robert C, Malhotra S, et al. An overview of benefits and risks of chronic melanocortin-1 receptor activation. J Eur Acad Dermatol Venereol, 2025, 39(1): 39-51.
46.	Wulf HC, Nissen CV, Philipsen PA. Inactivation of protoporphyrin IX in erythrocytes in patients with erythropoietic protoporphyria: a new treatment modality. Photodiagnosis Photodyn Ther, 2020, 29: 101582.
47.	Balwani M, Bonkovsky HL, Levy C, et al. Dersimelagon in erythropoietic protoporphyrias. N Engl J Med, 2023, 388(15): 1376-1385.

1. Chiara M, Primon I, Tarantini L, et al. Targeted resequencing of FECH locus reveals that a novel deep intronic pathogenic variant and eQTLs may cause erythropoietic protoporphyria (EPP) through a methylation-dependent mechanism. Genet Med, 2020, 22(1): 35-43.
2. Wu CK, Dailey HA, Rose JP, et al. The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis. Nat Struct Biol, 2001, 8(2): 156-160.
3. Phillips JD. Heme biosynthesis and the porphyrias. Mol Genet Metab, 2019, 128(3): 164-177.
4. Long ZB, Wang YW, Yang C, et al. Identification of FECH gene multiple variations in two Chinese patients with erythropoietic protoporphyria and a review. J Zhejiang Univ Sci B, 2016, 17(10): 813-820.
5. Lala SM, Naik H, Balwani M. Diagnostic delay in erythropoietic protoporphyria. J Pediatr, 2018, 202: 320-323.e2.
6. Coffey A, Leung DH, Quintanilla NM. Erythropoietic protoporphyria: initial diagnosis with cholestatic liver disease. Pediatrics, 2018, 141(Suppl 5): S445-S450.
7. Zhou SN, Xiao SX, Peng ZH, et al. A novel mutation of the FECH gene in a Chinese family with erythropoietic protoporphyria. J Dermatol Sci, 2007, 48(2): 145-147.
8. Zhang F, Lu L, Qian X, et al. Liver transplantation for erythropoietic protoporphyria with hepatic failure: a case report. Transplant Proc, 2008, 40(5): 1774-1776.
9. Kong XF, Ye J, Gao DY, et al. Identification of a ferrochelatase mutation in a Chinese family with erythropoietic protoporphyria. J Hepatol, 2008, 48(2): 375-379.
10. Lau KC, Lam CW, Fong B, et al. DNA-based diagnosis of erythropoietic protoporphyria in two families and the frequency of a low-expression FECH allele in a Chinese population. Clin Chim Acta, 2009, 400(1/2): 132-134.
11. Ma J, Xiao S, An J, et al. A novel splicing mutation and haplotype analysis of the FECH gene in a Chinese family with erythropoietic protoporphyria. J Eur Acad Dermatol Venereol, 2010, 24(6): 726-729.
12. Chuah SY, Tee SI, Pramono ZA, et al. Genetic study in a Singaporean patient with erythropoietic protoporphyria. Photodermatol Photoimmunol Photomed, 2012, 28(5): 269-271.
13. 彭瑩, 李浩賢, 劉靜, 等. 一例紅細胞生成性卟啉病報道//第十二次全國醫學遺傳學學術會議論文匯編. 鄭州: 中華醫學會醫學遺傳學分會, 中國遺傳學會人類和醫學遺傳學委員會, 2014: 105-106.
14. Cheung CY, Tam S, Lam CW, et al. Allogeneic haematopoietic stem cell transplantation for erythropoietic protoporphyria: a cautionary note. Blood Cells Mol Dis, 2015, 54(3): 266-267.
15. Alagappan U, Pramono ZA, Chong WS. Ferrochelatase gene mutation in Singapore and a novel frame-shift mutation in an Asian boy with erythropoietic protoporphyria. Int J Dermatol, 2017, 56(3): 272-276.
16. 李曉青, 師杰, 賴雅敏, 等. 4 例以黃疸為主要表現的紅細胞生成性原卟啉病臨床、病理及遺傳學分析. 臨床肝膽病雜志, 2017, 33(7): 1332-1335.
17. 馮靈美, 曹盼, 喬秀敏, 等. 以腹痛合并肝損傷為主要表現的紅細胞生成性原卟啉病. 中華消化雜志, 2017, 37(2): 123-125.
18. 曹麗麗, 董漪, 儲芳, 等. 以肝衰竭為主要表現的紅細胞生成性原卟啉病 1 例報告. 臨床肝膽病雜志, 2018, 34(9): 1975-1978.
19. 李東良, 方堅, 張志強, 等. 以肝硬化食管胃靜脈破裂出血就診的紅細胞生成性原卟啉病. 中華消化雜志, 2018, 38(4): 275-278.
20. Liu HM, Deng GH, Mao Q, et al. Diagnosis of erythropoietic protoporphyria with severe liver injury: a case report. World J Gastroenterol, 2019, 25(7): 880-887.
21. Jiang Z, Jiang X, Chen M. Severe aplastic anemia in a patient with erythropoietic protoporphyria successfully treated by avatrombopag. Ann Hematol, 2022, 101(6): 1361-1363.
22. 馬春苗, 于辛酉, 陸彪, 等. 兒童紅細胞生成性原卟啉病多器官功能衰竭一例并文獻復習. 中國全科醫學, 2021, 24(32): 4160-4163.
23. 馬莉, 李洪杰, 段雪飛. 以肝功能異常為主要表現的紅細胞生成性原卟啉病 1 例. 中國肝臟病雜志(電子版), 2021, 13(3): 68-72.
24. 楊秋萍, 李小紅, 聞娟, 等. 一例紅細胞生成性原卟啉病臨床分析及 FECH 基因檢測. 中國麻風皮膚病雜志, 2021, 37(4): 193-197.
25. 李會, 李晨, 劉曉燕, 等. 以肝硬化合并急性腹痛為表現的紅細胞生成性原卟啉病 1 例. 傳染病信息, 2021, 34(3): 282-286.
26. 孫鈺楨, 張江安, 于建斌, 等. 紅細胞生成性原卟啉病一家系基因突變分析. 中國皮膚性病學雜志, 2021, 35(4): 393-396, 412.
27. Zhao C, Guan JX, Hui DY, et al. Liver involvement in patients with erythropoietic protoporphyria: retrospective analysis of clinicopathological features of 5 cases. Ann Diagn Pathol, 2022, 56: 151859.
28. Huang HQ, Cai LQ, Li XH, et al. Diagnosis and treatment of icteric hepatitis caused by erythropoietic protoporphyria: a case report. Liver Res, 2022, 6(2): 116-120.
29. 李清清, 陳小燕, 王紅, 等. 成年女性紅細胞生成性原卟啉病合并甲狀腺功能亢進癥和肝功能障礙 1 例. 中南大學學報(醫學版), 2023, 48(11): 1768-1774.
30. Tan Q, Yang HF, Lan LF. Two novel mutations in FECH in a patient with erythropoietic protoporphyria: a case report. Int J Dermatol Venereol, 2023, 6(2): 112-114.
31. 謝瑩, 張源凈, 杭小鋒, 等. 以腹痛、黃疸、肝脾腫大為表現的紅細胞生成性原卟啉病 1 例. 肝臟, 2023, 28(2): 245-246.
32. Zeng T, Chen SR, Liu HQ, et al. Successful treatment of severe hepatic impairment in erythropoietic protoporphyria: a case report and review of literature. World J Hepatol, 2024, 16(6): 966-972.
33. Wu SH, Xiao T, Zhao D, et al. Case report: Xeroderma pigmentosum Group A with erythropoietic protoporphyria in a young Chinese patient. Front Endocrinol (Lausanne), 2024, 15: 1418254.
34. Wu X, Zhou X, Zhao S, et al. Treatment strategy for erythropoietic protoporphyria accompanied by severe abdominal pain and liver injury. Port Hypertens Cirrhos, 2024, 3: 36-38.
35. 吳振東, 周國強, 向燕, 等. 以肝硬化為主要表現的紅細胞生成性原卟啉病 1 例報告. 臨床肝膽病雜志, 2024, 40(3): 581-584.
36. Xiong HL, He S, Yang ZX, et al. Erythropoietic protoporphyria linked to intricate double heterozygous mutations in the FECH gene: a case report and literature review. Orphanet J Rare Dis, 2025, 20(1): 333.
37. Yang TT, Chen CX, Li CM, et al. Challenges in the pathological diagnosis of erythropoietic protoporphyria: a case report. Front Med (Lausanne), 2025, 12: 1664961.
38. Zhang YJ, Huang SP, Shang ZY, et al. Recurrent liver dysfunction in erythropoietic protoporphyria: a case with compound heterozygous FECH mutations. J Dig Dis, 2025, 26(5/6): 260-263.
39. Mizawa M, Makino T, Nakano H, et al. Erythropoietic protoporphyria in a Japanese population. Acta Derm Venereol, 2019, 99(7): 634-639.
40. Holme SA, Anstey AV, Finlay AY, et al. Erythropoietic protoporphyria in the U.K. : clinical features and effect on quality of life. Br J Dermatol, 2006, 155(3): 574-581.
41. Wahlin S, Floderus Y, St?l P, et al. Erythropoietic protoporphyria in Sweden: demographic, clinical, biochemical and genetic characteristics. J Intern Med, 2011, 269(3): 278-288.
42. Balwani M, Doheny D, Bishop DF, et al. Loss-of-function ferrochelatase and gain-of-function erythroid-specific 5-aminolevulinate synthase mutations causing erythropoietic protoporphyria and x-linked protoporphyria in North American patients reveal novel mutations and a high prevalence of X-linked protoporphyria. Mol Med, 2013, 19(1): 26-35.
43. Heerfordt IM, Lerche CM, Wulf HC. Trends in erythrocyte protoporphyrin IX concentration by age, sex and season among patients with erythropoietic protoporphyria-20 years of follow-up. Photodiagnosis Photodyn Ther, 2020, 32: 101928.
44. Barman-Aks?zen J, Minder EI, Schubiger C, et al. In ferrochelatase-deficient protoporphyria patients, ALAS2 expression is enhanced and erythrocytic protoporphyrin concentration correlates with iron availability. Blood Cells Mol Dis, 2015, 54(1): 71-77.
45. B?hm M, Robert C, Malhotra S, et al. An overview of benefits and risks of chronic melanocortin-1 receptor activation. J Eur Acad Dermatol Venereol, 2025, 39(1): 39-51.
46. Wulf HC, Nissen CV, Philipsen PA. Inactivation of protoporphyrin IX in erythrocytes in patients with erythropoietic protoporphyria: a new treatment modality. Photodiagnosis Photodyn Ther, 2020, 29: 101582.
47. Balwani M, Bonkovsky HL, Levy C, et al. Dersimelagon in erythropoietic protoporphyrias. N Engl J Med, 2023, 388(15): 1376-1385.

West China Medical Journal

Clinical characteristics and treatment exploration of patients with erythropoietic protoporphyria: a literature review and single-center case analysis

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