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Abstract：
Pseudoxanthoma elasticum (PXE), the prototype of heritable ectopic mineralization disorders, manifests with deposition of calcium hydroxyapatite crystals in the skin, eyes and arterial blood vessels. This autosomal recessive disorder, due to mutations in ABCC6, is usually diagnosed around the second decade of life. In the spectrum of heritable ectopic mineralization disorders are also generalized arterial calcification of infancy (GACI), with extremely severe arterial calcification diagnosed by prenatal ultrasound or perinatally, and arterial calcification due to CD73 deficiency (ACDC) manifesting with arterial and juxta-articular mineralization in the elderly; the latter disorders are caused by mutations in ENPP1 and NT5E, respectively. The unifying pathomechanistic feature in these three conditions is reduced plasma levels of inorganic pyrophosphate (PPi), a powerful endogenous inhibitor of ectopic mineralization. Several on-going attempts to develop treatments for these conditions, either with the goal to normalize PPi plasma levels or by means of preventing calcium hydroxyapatite deposition independent of PPi, are in advanced preclinical levels or in early clinical trials. This overview summarizes the prospects of treatment development for ectopic mineralization disorders, with PXE, GACI and ACDC as the target diseases, from the 2020 vantage point.
摘要：
弹性假性黄瘤（PXE），遗传性异位矿化障碍的原型，表现为钙羟基磷灰石晶体在皮肤中的沉积，眼睛和动脉血管。这种常染色体隐性疾病,由于ABCC6的突变，通常在生命的第二个十年左右被诊断出来。在遗传性异位矿化障碍的范围内，还包括婴儿期全身性动脉钙化（GACI），产前超声或围产期诊断出极其严重的动脉钙化，和CD73缺乏引起的动脉钙化（ACDC），表现为老年人的动脉和近关节矿化；后者的疾病是由ENPP1和NT5E突变引起的，分别。在这三种情况下，统一的病理机制特征是无机焦磷酸盐（PPi）的血浆水平降低，一种强大的内源性异位矿化抑制剂。一些正在进行的尝试来开发这些疾病的治疗方法，目标是使PPi血浆水平正常化，或者通过独立于PPi的防止羟基磷灰石钙沉积，处于先进的临床前水平或早期临床试验。本综述总结了异位矿化障碍的治疗发展前景。有了PXE,GACI和ACDC作为目标疾病，从2020年的有利位置。
