Research Progress in Pseudoxanthoma Elasticum and Related Ectopic Mineralization Disorders.
Research Progress in Pseudoxanthoma Elasticum and Related Ectopic Mineralization Disorders.
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DOI：
10.1016/j.jid.2015.10.065
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Uitto J
中科院分区：
文献类型：
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作者：
Li Q;Arányi T;Váradi A;Terry SF;Uitto J
遗传性异位矿化障碍代表一组表型多样的病症，其特征是磷酸钙复合物在软结缔组织中沉积。此类病症的原型是弹力假黄瘤（PXE），具有重叠临床特征的相关病症包括婴儿期全身动脉钙化（GACI）和CD73缺乏引起的动脉钙化（ACDC）。分子遗传学研究揭示了生理上参与无机焦磷酸盐 (PPi) 和磷酸盐 (Pi) 生成的基因突变，研究结果表明与 PPi/Pi 比率降低相关的统一病理机制。该假设基于以下概念：PPi 是矿化的强大抑制剂，而 Pi 是促矿化因子，并且适当的 PPi/Pi 比率对于在稳态条件下预防异位矿化至关重要。 PXE International 是首屈一指的患者支持组织，代表 PXE 患者和家属进行宣传，主办定期研究会议，评估这种疾病及相关异位矿化疾病的进展。最近的会议分别于 2014 年 9 月和 2015 年 9 月在马里兰州贝塞斯达和匈牙利布达佩斯举行。本报告根据这些会议的发言和讨论，总结了 PXE 和相关异位矿化障碍研究的最新进展，并对当前棘手的疾病具有药理学意义。
Heritable ectopic mineralization disorders represent a phenotypically diverse group of conditions characterized by deposition of calcium phosphate complexes in soft connective tissues. The prototype of such conditions is pseudoxanthoma elasticum (PXE), and related conditions with overlapping clinical features include generalized arterial calcification of infancy (GACI) and arterial calcification due to CD73 deficiency (ACDC). Molecular genetic investigations have revealed mutations in the genes physiologically involved in generation of inorganic pyrophosphate (PPi) and phosphate (Pi), and the findings suggest a unifying pathomechanism relating to reduced PPi/Pi ratio. This hypothesis is based on the notion that PPi serves as a powerful inhibitor of mineralization while Pi is a pro-mineralization factor, and an appropriate PPi/Pi ratio is critical for prevention of ectopic mineralization under homeostatic conditions. PXE International, the premiere patient support organization, advocating on behalf of patients and families with PXE, sponsors regular research meetings evaluating the progress in this and related ectopic mineralization disorders. The latest meetings were held in September 2014 in Bethesda, MD and in September 2015 in Budapest, Hungary. This report summarizes the latest progress in research on PXE and related ectopic mineralization disorders, based on presentations and discussions in these meetings, with pharmacologic implications for currently intractable disorders.