肿瘤钙质沉着症是一种由三个基因的突变引起的极其罕见的遗传性疾病,GALNT3、FGF23和KL,扰乱磷代谢.这种情况的标志是在关节周围的软组织中形成肿瘤。肿瘤钙质沉着症的其他表型特征是牙齿受累以及脑和血管钙化。本文报道的临床病例首次向科学界呈现c.202A>G(p。FGF23基因的Thr68Ala)突变,与高磷血症的肿瘤钙质沉着症和多个严重的血管动脉瘤相关。一名女性患者因其软组织中的肿瘤形成而接受了多次手术,首次出现在12个月大时。在这种情况下,患者被发现患有高磷酸盐血症,低磷酸盐清除率,随着总钙和离子钙的正常水平,肾小管的重吸收增加,维生素D3和甲状旁腺激素,用盐酸司维拉姆和低磷酸盐饮食治疗没有效果。在39岁时,由于水肿和颈部区域的脉动形成,患者接受了影像学检查,显示多血管动脉瘤伴血栓形成,为此她接受了手术和介入治疗。在这方面,由于已经建立的磷代谢紊乱,怀疑是遗传病。在这种情况下进行的358个基因的序列分析和缺失/重复测试显示,该女性是c.202A>G变体的纯合(p。FGF23基因的Thr68Ala)突变。已建立的突变不存在于群体数据库中。所呈现的临床病例是世界上第一个也是唯一一个证明这种类型的FGF23基因突变在肿瘤钙质沉着症的高磷酸盐变体的发展中的作用的病例,其特征是侵袭性形成多血管动脉瘤。
Tumoral calcinosis is an extremely rare genetic disease caused by mutations in three genes, GALNT3, FGF23, and KL, which disrupt phosphorus metabolism. The hallmark of this condition is the formation of tumors in the soft tissues around the joints. Other phenotypic features of tumoral calcinosis are dental involvement and brain and vascular calcifications. The clinical case reported herein presents for the first time to the scientific community the c.202A>G (p.Thr68Ala) mutation of the FGF23 gene, associated with a hyperphosphatemic variant of tumoral calcinosis and multiple severe vascular aneurysms. A female patient underwent multiple surgeries for tumor formations in her soft tissues that first appeared at the age of 12 months. On this occurrence, the patient was found to have hyperphosphatemia, low phosphate clearance, increased tubular reabsorption with normal levels of total and ionized calcium, vitamin D3, and parathyroid hormone, and no effect of treatment with sevelamer hydrochloride and a low-phosphate diet. At the age of 39, the patient underwent imaging studies due to edema and a pulsating formation in the neck area, which revealed multiple vascular aneurysms with thrombosis, for which she received operative and interventional treatment. In this connection, and because of the established phosphorus metabolism disturbance, a genetic disease was suspected. The sequence analysis and deletion/duplication testing of the 358 genes performed on this occasion revealed that the woman was homozygous for a variant of the c.202A>G (p.Thr68Ala) mutation of the FGF23 gene. The established mutation is not present in population databases. The presented clinical case is the first and only one in the world to demonstrate the role of this type of FGF23 gene mutation in the development of a hyperphosphatemic variant of tumoral calcinosis characterized by aggressive formation of multiple vascular aneurysms.