Huynh Carson, Gillis Andrea, Fazendin Jessica, Abdullatif Hussein
University of Alabama at Birmingham Department of Pediatrics, United States of America.
University of Alabama at Birmingham Department of Surgery, United States of America.
Bone Rep. 2022 Jul 20;17:101605. doi: 10.1016/j.bonr.2022.101605. eCollection 2022 Dec.
Epidermal Nevus Syndrome (ENS), also known as Cutaneous Skeletal Hypophosphatemia Syndrome or Linear Sebaceous Nevus Syndrome, is caused by a mosaic somatic mutation of (Rat Sarcoma genes) which leads to abnormally elevated levels of fibroblast growth factor 23 (FGF23). FGF23 is a major regulator in phosphate homeostasis. There are multiple disorders, along with Epidermal Nevus Syndrome (ENS), that result in unusually high circulating levels of FGF23. This increase ultimately leads to renal phosphate wasting and reduced levels of 1,25-dihydroxy vitamin D. Across these disorders, the clinical symptoms are similar and often include osteomalacia (hypophosphatemic rickets in children), muscle weakness, fatigue, joint deformities, bone pain, and fractures. Burosumab (KRN23), is an IgG1 monoclonal antibody that binds to the FGF23 receptor and inhibits the activity of FGF23. This leads to an increase in serum phosphate levels. Burosumab emerged as a potential therapy in FGF23 overactivity disorders. Burosumab was successful in the treatment of X-linked hypophosphatemia (XLH) and is now FDA-approved for its treatment. Studies have indicated that Burosumab therapy in subjects with XLH consistently increases and sustains serum phosphorus levels and tubular reabsorption of phosphate without a major impact on urine calcium levels or vitamin D metabolism. We studied the effect of Burosumab treatment in a single pediatric patient with Epidermal Nevus Syndrome. Serum phosphorus rose gradually as we titrated the dose of Burosumab upwards. During treatment, a persistent elevation of parathyroid hormone levels was noted along with a persistent elevation of serum calcium. We presumed the patient had tertiary hyperparathyroidism. However, after the removal of three parathyroid glands, the pathology came back with a single enlarged parathyroid adenoma. Subsequently, his calcium and PTH, and phosphorus levels stabilized while taking only Burosumab. ClinicalTrials.gov NCT04320316.
表皮痣综合征（ENS），也被称为皮肤骨骼低磷血症综合征或线状皮脂腺痣综合征，由（大鼠肉瘤基因）的镶嵌体细胞突变引起，该突变导致成纤维细胞生长因子23（FGF23）水平异常升高。FGF23是磷酸盐稳态的主要调节因子。除了表皮痣综合征（ENS）外，还有多种疾病会导致循环中FGF23水平异常升高。这种升高最终会导致肾脏磷酸盐流失以及1,25 - 二羟基维生素D水平降低。在这些疾病中，临床症状相似，通常包括骨软化症（儿童低磷性佝偻病）、肌肉无力、疲劳、关节畸形、骨痛和骨折。布罗索尤单抗（KRN23）是一种IgG1单克隆抗体，它与FGF23受体结合并抑制FGF23的活性。这会导致血清磷酸盐水平升高。布罗索尤单抗成为FGF23活性过高疾病的一种潜在治疗方法。布罗索尤单抗成功治疗了X连锁低磷血症（XLH），现已获得美国食品药品监督管理局（FDA）批准用于该疾病的治疗。研究表明，布罗索尤单抗治疗XLH患者能持续提高并维持血清磷水平以及肾小管对磷酸盐的重吸收，而对尿钙水平或维生素D代谢没有重大影响。我们研究了布罗索尤单抗治疗一名患有表皮痣综合征的儿科患者的效果。随着我们逐步增加布罗索尤单抗的剂量，血清磷逐渐升高。在治疗过程中，发现甲状旁腺激素水平持续升高，同时血清钙也持续升高。我们推测该患者患有三发性甲状旁腺功能亢进症。然而，在切除三个甲状旁腺后，病理检查结果显示为单个增大的甲状旁腺腺瘤。随后，在仅服用布罗索尤单抗时，他的钙、甲状旁腺激素和磷水平稳定下来。ClinicalTrials.gov标识符：NCT04320316。
