Basal ganglia calcification: 'Fahr's disease'

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Brain calcification, particularly basal ganglia calcification, presents a broad differential diagnosis.
• Primary familial brain calcification (PFBC), previously known as Fahr's disease, is a neurological disorder characterized by bilateral, symmetrical calcium-hydroxyapatite crystal deposition in the brain.
• PFBC has a presumed genetic etiology and manifests with diverse motor, cognitive, and psychiatric symptoms.

Purpose of the Study:

• To provide a comprehensive overview of Primary Familial Brain Calcification (PFBC).
• To detail the phenotypic spectrum, diagnostic approaches, etiopathogenesis, and management strategies for PFBC.
• To highlight recent advancements in understanding the genetic basis and underlying mechanisms of PFBC.

Main Methods:

• Review of genetic studies linking specific genes to PFBC.
• Analysis of identified pathomechanisms including phosphate dyshomeostasis and blood-brain barrier integrity.
• Synthesis of current knowledge on clinical features, diagnosis, and treatment.

Main Results:

• Seven genes associated with PFBC have been identified since 2012, with autosomal dominant or recessive inheritance patterns.
• Converging pathomechanisms involve inorganic phosphate dyshomeostasis, impaired endothelial function, and disrupted blood-brain barrier integrity.
• Genetic discoveries have significantly advanced the understanding of PFBC pathogenesis.

Conclusions:

• PFBC is a genetically heterogeneous disorder with identifiable molecular pathways.
• Understanding these pathomechanisms provides potential targets for novel, disease-modifying therapies.
• A comprehensive approach integrating genetic, clinical, and pathomechanistic insights is crucial for managing PFBC.