TY - JOUR
T1 - Mechanisms of calcification in Fahr disease and exposure of potential therapeutic targets
AU - Peters, Melissa E M
AU - de Brouwer, Esther J M
AU - Bartstra, Jonas W
AU - Mali, Willem P Th M
AU - Koek, Huiberdina L
AU - Rozemuller, Annemieke J M
AU - Baas, Annette F
AU - de Jong, Pim A
N1 - Publisher Copyright:
© 2023 American Academy of Neurology.
PY - 2020/10
Y1 - 2020/10
N2 - Purpose of review: 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.Recent findings: 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 SLC20A2 and XPR1 lead to a disrupted phosphate metabolism involving brain-specific inorganic phosphate transporters. Mutations in PDGFB and PDGFRB are associated with disrupted blood-brain barrier integrity and dysfunctional pericyte maintenance. In addition, the MYORG gene has recently been discovered to be involved in the autosomal recessive inheritance of Fahr.Summary: Knowledge about the mutations and corresponding pathways may expose therapeutic opportunities for patients with Fahr disease and vascular calcifications in the brain in general.
AB - Purpose of review: 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.Recent findings: 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 SLC20A2 and XPR1 lead to a disrupted phosphate metabolism involving brain-specific inorganic phosphate transporters. Mutations in PDGFB and PDGFRB are associated with disrupted blood-brain barrier integrity and dysfunctional pericyte maintenance. In addition, the MYORG gene has recently been discovered to be involved in the autosomal recessive inheritance of Fahr.Summary: Knowledge about the mutations and corresponding pathways may expose therapeutic opportunities for patients with Fahr disease and vascular calcifications in the brain in general.
UR - http://www.scopus.com/inward/record.url?scp=85133980283&partnerID=8YFLogxK
U2 - 10.1212/CPJ.0000000000000782
DO - 10.1212/CPJ.0000000000000782
M3 - Review article
C2 - 33299674
SN - 2163-0402
VL - 10
SP - 449
EP - 457
JO - Neurology: Clinical Practice
JF - Neurology: Clinical Practice
IS - 5
ER -