Peters Melissa E M, de Brouwer Esther J M, Bartstra Jonas W, Mali Willem P Th M, Koek Huiberdina L, Rozemuller Annemieke J M, Baas Annette F, de Jong Pim A
Departments of Radiology (MEMP, JWB, WPTMM, PAdJ), Geriatrics (EJMdB, HLK), Pathology (AJMR), and Genetics (AFB), University Medical Center Utrecht, The Netherlands.
Neurol Clin Pract. 2020 Oct;10(5):449-457. doi: 10.1212/CPJ.0000000000000782.
There is growing interest in disorders involved in ectopic mineralization. Fahr disease or idiopathic basal ganglia calcification can serve as a model for ectopic mineralization in the basal ganglia, which is fairly common in the general population. In this review, we will focus on causative gene mutations and corresponding pathophysiologic pathways in Fahr disease.
Patients with Fahr disease have a variability of symptoms, such as movement disorders, psychiatric signs, and cognitive impairment, but can also be asymptomatic. Fahr disease is mostly autosomal dominant inherited, and there are mutations found in 4 causative genes. Mutations in and lead to a disrupted phosphate metabolism involving brain-specific inorganic phosphate transporters. Mutations in and are associated with disrupted blood-brain barrier integrity and dysfunctional pericyte maintenance. In addition, the gene has recently been discovered to be involved in the autosomal recessive inheritance of Fahr.
Knowledge about the mutations and corresponding pathways may expose therapeutic opportunities for patients with Fahr disease and vascular calcifications in the brain in general.
人们对涉及异位矿化的疾病越来越感兴趣。法尔病或特发性基底节钙化可作为基底节异位矿化的一个模型，这种情况在普通人群中相当常见。在本综述中，我们将重点关注法尔病的致病基因突变及相应的病理生理途径。
法尔病患者症状多样，如运动障碍、精神症状和认知障碍，但也可能无症状。法尔病大多为常染色体显性遗传，已在4个致病基因中发现突变。其中两个基因的突变导致涉及脑特异性无机磷酸盐转运体的磷酸盐代谢紊乱。另外两个基因的突变与血脑屏障完整性破坏和周细胞维持功能障碍有关。此外，最近发现该基因与法尔病的常染色体隐性遗传有关。
关于这些突变及相应途径的知识可能为法尔病患者以及一般脑内血管钙化患者带来治疗机会。
