OBJECTIVE

Primary Familial Brain Calcification (PFBC) is a rare neurodegenerative disorder characterized by small vessel calcifications in the basal ganglia. PFBC is caused by pathogenic variants in different genes and its physiopathology is still largely unknown. Skin vascular calcifications have been detected in single PFBC cases, suggesting that calcium deposition may not be limited to the brain, but it is unknown whether this is a hallmark of all PFBC genetic and clinical subtypes. This work aims at assessing anatomical and subcellular localization of calcium-phosphate deposits in skin biopsies from PFBC patients to ascertain the accuracy of histological calcium staining in differentiating PFBC from healthy controls (HC) and Parkinson's Disease (PD).

METHODS

Histopathology and light microscopy of skin biopsy from 20 PFBC, 7 HC and 10 PD subjects (3 mm ø-5 mm deep punch biopsies, Hematoxylin-Eosin and vonKossa staining, immunoperoxidase CD31 staining); clinical, genetic and radiological assessment.

RESULTS

Unlike HC and PD subjects, the majority of PFBC patients (17/20) showed a consistent pattern of granular argyrophilic calcium-phosphate deposits in the basal lamina and the cytoplasm of CD31+ endothelial cells and pericytes of dermal capillaries, and the basement membrane of sweat glands. This pattern was unrelated to the underlying mutated gene or clinical status.

INTERPRETATION

Skin biopsy may be a novel PFBC diagnostic tool and a potential biomarker for future therapies, and a tool to investigate PFBC disease mechanisms. Different findings in some patients could be due to skin sampling variability and biological consequences of specific PFBC gene variants.