Soufleris Stephen, Moore Michelle, Phillips John D, Netzel Brian, Rudnick Sean, Faust Denise, Bonkovsky Herbert L
Division of Gastroenterology and Hepatology, Department of Medicine, Wake Forest University School of Medicine/Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
Division of Hematology, Department of Medicine, University of Utah Health Science Center, Salt Lake City, UT, USA.
AME Case Rep. 2024 May 24;8:67. doi: 10.21037/acr-23-66. eCollection 2024.
Porphyria cutanea tarda (PCT) is usually caused by acquired defects in uroporphyrinogen decarboxylase (UROD) activity in the liver. This more common form of PCT is called type 1 PCT. Major known risk factors for PCT include iron overload, such as occurs due to mutations in HFE, associated with classical hereditary hemochromatosis, chronic hepatitis C infection, heavy alcohol use, tobacco use, and estrogen therapy. In addition, in about 25% of patients with PCT, namely, those with PCT type 2, an inherited partial defect in UROD activity is found. In such persons, this partial defect, which is found in all cells, including hepatocytes, red blood cells, and others, contributes to the development of biochemically and clinically active disease.
Herein we describe salient features of a man in his eighth decade of life with onset of clinical PCT. Among risk factors were heavy alcohol and tobacco use. Genetic testing revealed a novel mutation in one of his alleles of the gene, namely, c.224 G>C; p. Arg 75 Pro, and enzymatic testing revealed that red blood cell UROD activity was decreased by 50%. This mutation in the gene is predicted to have a major effect on protein structure and function, confirmed by the 50% decrease in activity of the enzyme.
The previously undescribed mutation in found in this man, namely, c.224 G>C; p. Arg 75 Pro is pathogenic.
迟发性皮肤卟啉症（PCT）通常由肝脏中尿卟啉原脱羧酶（UROD）活性的后天缺陷引起。这种更常见的PCT形式称为1型PCT。已知的PCT主要危险因素包括铁过载，如因HFE基因突变所致，与经典遗传性血色素沉着症相关、慢性丙型肝炎感染、大量饮酒、吸烟和雌激素治疗。此外，在约25%的PCT患者中，即2型PCT患者，发现存在UROD活性的遗传性部分缺陷。在这些人中，这种在包括肝细胞、红细胞等所有细胞中发现的部分缺陷，促成了生化和临床活性疾病的发展。
在此我们描述一名八十多岁临床诊断为PCT男性的显著特征。危险因素包括大量饮酒和吸烟。基因检测显示其一个等位基因存在新突变，即c.224 G>C；p.Arg 75 Pro，酶学检测显示红细胞UROD活性降低了50%。该基因的这种突变预计会对蛋白质结构和功能产生重大影响，酶活性降低50%证实了这一点。
在该男性中发现的先前未描述的基因（c.224 G>C；p.Arg 75 Pro）突变具有致病性。
