Hospital Italiano de Buenos Aires, Buenos Aires, Argentina;
Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Pediatrics. 2019 Aug;144(2). doi: 10.1542/peds.2018-2922.
Juvenile polyposis syndrome is a rare autosomal dominant condition characterized by multiple hamartomatous polyps throughout the gastrointestinal tract. Juvenile polyposis of infancy is a generalized severe form of juvenile polyposis syndrome associated with a poor prognosis. A 47-month-old female infant presented initially with gastrointestinal bleeding and protein-losing enteropathy at 4 months of age. At the age of 12 months, the condition worsened, requiring albumin infusions every 24 to 48 hours and red blood cell transfusions every 15 days. Upper gastrointestinal endoscopy, colonoscopy, and small-bowel enteroscopy revealed diffuse polyposis that was treated with multiple endoscopic polypectomies. Despite subtotal colectomy with ileorectal anastomosis, protein-losing enteropathy and bleeding persisted, requiring continued blood transfusions and albumin infusions. A chromosomal microarray revealed a single allele deletion in chromosome 10q23, involving both the and genes. Loss of function is associated with an increased activation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway involved in cell proliferation. Treatment with sirolimus, an mTOR inhibitor, was initiated with the aim of inhibiting polyp growth. Soon after initiation of treatment with sirolimus, blood and albumin infusions were no longer needed and resulted in improved patient growth and quality of life. This case represents the first detailed report of successful drug therapy for life-threatening juvenile polyposis of infancy.
幼年性息肉综合征是一种罕见的常染色体显性遗传疾病，其特征是胃肠道内存在多个错构瘤性息肉。婴儿型幼年性息肉是一种与预后不良相关的幼年性息肉综合征的广泛严重形式。一位 47 月龄的女性婴儿，最初在 4 月龄时出现胃肠道出血和蛋白丢失性肠病，12 月龄时病情恶化，需要每 24-48 小时输注白蛋白，每 15 天输注红细胞。上消化道内镜、结肠镜和小肠内镜检查显示弥漫性息肉，行多次内镜息肉切除术治疗。尽管进行了结肠次全切除加回肠直肠吻合术，但蛋白丢失性肠病和出血仍持续存在，需要持续输血和输注白蛋白。染色体微阵列分析显示 10q23 染色体上的单个等位基因缺失，涉及 和 基因。 功能丧失与蛋白激酶 B（AKT）/雷帕霉素靶蛋白（mTOR）通路的活性增加有关，该通路参与细胞增殖。为了抑制息肉生长，开始使用 mTOR 抑制剂西罗莫司进行治疗。西罗莫司治疗开始后不久，就不再需要输血和输注白蛋白，患者的生长和生活质量得到改善。该病例代表了首例成功的药物治疗婴儿型致命性幼年性息肉的详细报告。
