Mechanisms of calcification in Fahr disease and exposure of potential therapeutic targets.

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 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.

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.