Shah Nischay, Bhatt Harshil
University Hospitals Richmond Med Center
Goshen Hospital
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease that presents clinically with a variety of symptoms, the most prevalent of which are hemolytic anemia, hemoglobinuria, and somatic symptoms including fatigue and shortness of breath. Other findings associated with PNH include thrombosis, renal insufficiency, and in the later course of the disease, even bone marrow failure. The condition is genetic, with the mutations occurring on the X linked gene. While the term paroxysmal nocturnal hemoglobinuria was introduced by Enneking in 1925, case reports dating back to the 1880s can be found. One of the earliest was that of Strubing, who documented the case of a young adult man with fatigue, abdominal pain, and intermittent hemoglobinuria. Strubing also noted that the patient's plasma was red following the most severe episodes, and he deduced that intravascular hemolysis was the cause. Later in 1937, Ham was able to discover that erythrocytes of individuals with PNH hemolyzed when incubated with normal acidified urine. This resulted in the first diagnostic test for PNH, known as the Ham test (acidified serum test). While complement activation was suspected as the etiology for hemolysis, the theory was not formally proven until 1954. Over the following years, the nature of protein deficiencies affecting PNH erythrocytes was identified, and this paved the way for the identification of the responsible genetic mutation. Although PNH is a rare condition, it has a significant impact on the quality of life of a patient. About 4 or 5 decades ago 10-year survival for this condition was only 50 percent. However, in the last 15 years, advances in treatment such as the development of eculizumab have improved survival to more than 75 percent.
阵发性夜间血红蛋白尿（PNH）是一种罕见疾病，临床上表现为多种症状，其中最常见的是溶血性贫血、血红蛋白尿以及包括疲劳和呼吸急促在内的躯体症状。与PNH相关的其他表现包括血栓形成、肾功能不全，在疾病后期甚至会出现骨髓衰竭。该病是遗传性的，突变发生在X连锁基因上。虽然“阵发性夜间血红蛋白尿”这一术语由恩内金于1925年提出，但可以找到可追溯到19世纪80年代的病例报告。最早的病例之一是施特鲁宾的报告，他记录了一名年轻成年男性出现疲劳、腹痛和间歇性血红蛋白尿的病例。施特鲁宾还指出，在最严重的发作后患者的血浆呈红色，他推断血管内溶血是病因。1937年晚些时候，哈姆发现PNH患者的红细胞在与正常酸化尿液孵育时会发生溶血。这导致了首个针对PNH的诊断测试，即哈姆试验（酸化血清试验）。虽然怀疑补体激活是溶血的病因，但直到1954年该理论才得到正式证实。在接下来的几年里，确定了影响PNH红细胞的蛋白质缺陷的性质，这为识别相关基因突变铺平了道路。尽管PNH是一种罕见疾病，但它对患者的生活质量有重大影响。大约四五十年前，这种疾病的10年生存率仅为50%。然而，在过去15年里，诸如依库珠单抗等治疗方法的进步使生存率提高到了75%以上。
