Division of Oncogenetics, The Netherlands Cancer Institute, 1066CX Amsterdam, The Netherlands.
Institute of Enzymology, Research Center for Natural Sciences (RCNS), Hungarian Academy of Sciences, 1117 Budapest, Hungary.
Trends Biochem Sci. 2019 Feb;44(2):125-140. doi: 10.1016/j.tibs.2018.10.005. Epub 2018 Nov 13.
Ever since Garrod deduced the existence of inborn errors in 1901, a vast array of metabolic diseases has been identified and characterized in molecular terms. In 2018 it is difficult to imagine that there is any uncharted backyard left in the metabolic disease landscape. Nevertheless, it took until 2013 to identify the cause of a relatively frequent inborn error, pseudoxanthoma elasticum (PXE), a disorder resulting in aberrant calcification. The mechanism found was not only biochemically interesting but also points to possible new treatments for PXE, a disease that has remained untreatable. In this review we sketch the tortuous road that led to the biochemical understanding of PXE and to new ideas for treatment. We also discuss some of the controversies still haunting the field.
自 1901 年 Garrod 推断出先天缺陷的存在以来，已经在分子水平上鉴定和描述了大量的代谢疾病。2018 年，很难想象代谢疾病领域还有任何未知的后院。然而，直到 2013 年，才确定了一种相对常见的先天缺陷——弹性假黄瘤（PXE）的病因，这是一种导致异常钙化的疾病。发现的机制不仅在生化上很有趣，而且也为 PXE 这种仍然无法治疗的疾病提供了新的治疗方法。在这篇综述中，我们简要描述了导致对 PXE 的生化理解以及治疗新想法的曲折道路。我们还讨论了一些仍然困扰该领域的争议。
