弹性假性黄瘤(PXE)是一种由ABCC6基因突变引起的常染色体隐性遗传的遗传代谢疾病。功能性ABCC6蛋白的缺乏导致异位矿化,这在皮肤的弹性组织中最为明显,眼睛和血管。PXE的临床患病率估计在1/100,000和1/25,000之间,女性占主导地位。PXE的第一个临床体征几乎总是在颈项和颈部两侧以及弯曲区域的小黄色丘疹。丘疹合并,皮肤变得松弛和起皱。真皮中部弹性纤维很短,支离破碎,结块钙化.布鲁赫膜营养不良钙化,血管样条纹显示,可能引发脉络膜新生血管,最终,晚期疾病的中心视力丧失和失明。中小型动脉壁的病变可能导致间歇性跛行和外周动脉疾病。心脏并发症(心肌梗塞,心绞痛)被认为相对罕见,但值得彻底调查。已经报道了缺血性中风。PXE是一种代谢疾病,其中抗矿化因子的循环水平低。有充分的证据表明,该因素是无机焦磷酸盐(PPi),循环低水平的PPi和降低的PPi/Pi比率是由于缺乏携带突变ABCC6蛋白的肝细胞释放ATP所致。然而,结合的底物,由ABCC6蛋白转运或调节仍然未知。已经鉴定了ABCC6基因的300多种序列变体。目前尚无治愈PXE的方法;主要对症治疗是血管内皮生长因子抑制剂治疗(用于眼科表现),生活方式,降脂和饮食措施(减少血管危险因素),和血管手术(用于严重的心血管表现)。未来的治疗选择可能包括基因治疗/编辑和药物伴侣治疗。
Pseudoxanthoma elasticum (PXE) is a genetic metabolic disease with autosomal recessive inheritance caused by mutations in the ABCC6 gene. The lack of functional ABCC6 protein leads to ectopic mineralization that is most apparent in the elastic tissues of the skin, eyes and blood vessels. The clinical prevalence of PXE has been estimated at between 1 per 100,000 and 1 per 25,000, with slight female predominance. The first clinical sign of PXE is almost always small yellow papules on the nape and sides of the neck and in flexural areas. The papules coalesce, and the skin becomes loose and wrinkled. The mid-dermal elastic fibers are short, fragmented, clumped and calcified. Dystrophic calcification of Bruch\'s membrane, revealed by angioid streaks, may trigger choroidal neovascularization and, ultimately, loss of central vision and blindness in late-stage disease. Lesions in small and medium-sized artery walls may result in intermittent claudication and peripheral artery disease. Cardiac complications (myocardial infarction, angina pectoris) are thought to be relatively rare but merit thorough investigation. Ischemic strokes have been reported. PXE is a metabolic disease in which circulating levels of an anti-mineralization factor are low. There is good evidence to suggest that the factor is inorganic pyrophosphate (PPi), and that the circulating low levels of PPi and decreased PPi/Pi ratio result from the lack of ATP release by hepatocytes harboring the mutant ABCC6 protein. However, the substrate(s) bound, transported or modulated by the ABCC6 protein remain unknown. More than 300 sequence variants of the ABCC6 gene have been identified. There is no cure for PXE; the main symptomatic treatments are vascular endothelial growth factor inhibitor therapy (for ophthalmic manifestations), lifestyle, lipid-lowering and dietary measures (for reducing vascular risk factors), and vascular surgery (for severe cardiovascular manifestations). Future treatment options may include gene therapy/editing and pharmacologic chaperone therapy.