Physiological Calcification Research Articles

Age-Associated Calcification: Insights from Murine Models

Calcification refers to the deposition of calcium-containing crystals either intracellularly or within the extracellular matrix. Physiologic calcification is a normal process occurring during bone and tooth development and growth. In contrast, pathologic calcification occurs in soft tissues that typically do not undergo mineralization, such as blood vessels, cartilage, tendons, and skin. Pathological calcification is significantly associated with tissue impairment and the development of secondary diseases, such as atherosclerosis, osteoarthritis, tendinopathy, and skin ulcers. Aging, a natural process linked to numerous pathologic conditions, is one of the most recognized risk factors for pathological calcification. In this manuscript, we review the current state of knowledge regarding the role of aging in calcification across different tissues. We focus on the mechanisms activated during normal aging, including cellular senescence, decreased pyrophosphate levels, increased secretion of extracellular vesicles, elevated oxidative stress, and higher levels of pro-mineralizing cytokines, all of which can contribute to pathological calcification. Finally, we discuss the available animal models used to study the impact of aging on calcification.

Converging Mechanisms of Vascular and Cartilaginous Calcification.

Physiological calcification occurs in bones and epiphyseal cartilage as they grow, whereas ectopic calcification occurs in blood vessels, cartilage, and soft tissues. Although it was formerly thought to be a passive and degenerative process associated with aging, ectopic calcification has been identified as an active cell-mediated process resembling osteogenesis, and an increasing number of studies have provided evidence for this paradigm shift. A significant association between vascular calcification and cardiovascular risk has been demonstrated by various studies, which have shown that arterial calcification has predictive value for future coronary events. With respect to cartilaginous calcification, calcium phosphate or hydroxyapatite crystals can form asymptomatic deposits in joints or periarticular tissues, contributing to the pathophysiology of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, tendinitis, and bursitis. The risk factors and sequence of events that initiate ectopic calcification, as well as the mechanisms that prevent the development of this pathology, are still topics of debate. Consequently, in this review, we focus on the nexus of the mechanisms underlying vascular and cartilaginous calcifications, trying to circumscribe the similarities and disparities between them to provide more clarity in this regard.

Bone Marrow–Derived ABCC6 Is an Essential Regulator of Ectopic Calcification In Pseudoxanthoma Elasticum

Physiological calcification of soft tissues is a common occurrence in aging and various acquired and inherited disorders. ABCC6 sequence variations cause the calcification phenotype of pseudoxanthoma elasticum (PXE) as well as some cases of generalized arterial calcification of infancy, which is otherwise caused by defective ENPP1. ABCC6 is primarily expressed in the liver, which has given the impression that the liver is central to the pathophysiology of PXE/generalized arterial calcification of infancy. The emergence of inflammation as a contributor to the calcification in PXE suggested that peripheral tissues play a larger role than expected. In this study, we investigated whether bone marrow-derived ABCC6 contributes to the calcification in PXE. In Abcc6‒/‒ mice, we observed prevalent mineralization in several lymph nodes and surrounding connective tissues and an extensive network of lymphatic vessels within vibrissae, a calcified tissue in Abcc6‒/‒ mice. Furthermore, we found evidence of lymphangiogenesis in patients with PXE and mouse skin, suggesting an inflammatory process. Finally, restoring wild-type bone marrow in Abcc6‒/‒ mice produced a significant reduction of calcification, suggesting that the liver alone is not sufficient to fully inhibit mineralization. With evidence that ABCC6 is expressed in lymphocytes, wesuggest that the adaptative immune system and inflammation largely contribute to the calcification in PXE/generalized arterial calcification of infancy.

Inhibiting Lysyl Oxidases prevents pathologic cartilage calcification

Lysyl oxidases (LOX(L)) are enzymes that catalyze the formation of cross-links in collagen and elastin fibers during physiologic calcification of bone. However, it remains unknown whether they may promote pathologic calcification of articular cartilage, an important hallmark of debilitating arthropathies. Here, we have studied the possible roles of LOX(L) in cartilage calcification, related and not related to their cross-linking activity. We first demonstrated that inhibition of LOX(L) by β-aminoproprionitrile (BAPN) significantly reduced calcification in murine and human chondrocytes, and in joint of meniscectomized mice. These BAPN’s effects on calcification were accounted for by different LOX(L) roles. Firstly, reduced LOX(L)-mediated extracellular matrix cross-links downregulated Anx5, Pit1 and Pit2 calcification genes. Secondly, BAPN reduced collagen fibrotic markers Col1 and Col3. Additionally, LOX(L) inhibition blocked chondrocytes hypertrophic differentiation (Runx2 and COL10), pro-inflammatory IL-6 release and reactive oxygen species (ROS) production, all triggers of chondrocyte calcification. Through unbiased transcriptomic analysis we confirmed a positive correlation between LOX(L) genes and genes for calcification, hypertrophy and extracellular matrix catabolism. This association was conserved throughout species (mouse, human) and tissues that can undergo pathologic calcification (kidney, arteries, skin). Overall, LOX(L) play a critical role in the process of chondrocyte calcification and may be therapeutic targets to treat cartilage calcification in arthropathies.

Precise Starving Therapy via Physiologically Dependent Photothermal Conversion Promoted Mitochondrial Calcification Based on Multi‐Functional Gold Nanoparticles for Effective Tumor Treatment

AbstractStarving therapy based on tumor calcification has been considered as a promising strategy with high biosafety for tumor treatment. However, the limited calcium (Ca2+) concentration in/around tumor tissue as well as the slow and uncontrollable process of the physiological calcification are all challenges for its application. Herein, a sialic acid (SA, Ca2+ chelator), folic acid (FA, tumor targeting agent) and triphenylphosphine (TPP, mitochondrial targeting agent) co‐modified gold nanoparticles (SFT‐Au) are fabricated to take advantage of the abundant Ca2+ in mitochondria as well as the Ca2+ collection and Ca2+ dependent photothermal property of SFT‐Au to achieve a precise and promoted calcification of tumor mitochondria for effective starving therapy. During therapy, the SFT‐Au will first accumulate in tumor mitochondria through stepwise targeting processes medicated by FA and TPP. After that, the SA further binds with the over‐expressed Ca2+ in tumor mitochondria to induce the aggregation of SFT‐Au, which not only gathers Ca2+ to initiate the calcification of mitochondria, but in situ generates photothermal agent to perform photothermal conversion under 808 nm irradiation to promote the calcification, resulting in effective prohibition of the energy metabolism in tumor cells for starving therapy and continuously photothermal damage of tumor cells to enhance the therapeutic efficiency.

Responsive calcium-derived nanoassemblies induce mitochondrial disorder to promote tumor calcification.

Physiological calcification of the treated tumor area is considered to be a predictor of good prognosis. Promoting tumor calcification by inducing mitochondrial metabolic disorder and destroying calcium equilibrium has a potential inhibitory effect on tumor proliferation. Here, by promoting calcification by inducing mitochondrial dysfunction combined with triggering a surge of reactive oxygen species, we construct a bioresponsive calcification initiator, termed CaP-AA, using CaHPO4 covalently doped l-ascorbic acid. CaHPO4 releases Ca2+ within the cytoplasm of tumor cells to trigger calcium overload. Meanwhile, exogenous l-ascorbic acid indirectly enhances metabolic balance disruption via pro-oxidant effects. Such Ca2+ overload increases the likelihood of tumor calcification in vivo for tumor inhibition by perturbing mitochondrial homeostasis. The introduction of responsive calcium sources that would, in turn, trigger intratumoral calcification mediated by perturbing mitochondrial homeostasis would be an effective regulatory strategy for tumor therapy.

Physiologic intracranial calcifications incidentally detected on cone beam computed tomography

This study aims to determine the incidence of physiologic intracranial calcifications on cone beam computed tomography (CBCT) and to contribute to the differentiation between physiologic and pathologic intracranial calcifications by sharing their characteristic appearances, with the largest number of patients in the literature and many different types of physiologic calcifications. CBCT images of 996 patients admitted to the clinic between 2018 and 2019 were scanned retrospectively. Petroclinoid (PCL) and interclinoid ligaments (ICL), pineal gland, coronoid plexus, falx cerebri, tentorium cerebelli, and other dural calcifications were evaluated in each radiograph. Physiologic calcification was present in 49.4% of the cases, and pineal gland calcification was the most common (47.6%) type. PCL calcification was detected in 22.1%, and it was mostly bilateral partial. There were complete ICL in 1.2%, coronoid plexus in 11.3%, falx cerebri in 6.3%, tentorium cerebelli in 1.1%, and other dural calcifications in 3.6%. Only PCL calcifications differed between sexes and were more common in males. PCL, pineal gland, and coronoid plexus calcifications were most detected in the third decade of the cases. Intracranial calcifications are detected incidentally in CBCT examinations. Some calcifications may indicate pathologic conditions, and patients may need to be referred for further evaluation.

Frequency, shape, and estimated volume of intracranial physiologic calcification in different age groups investigated by brain computed tomography scan: a retrospective study.

Intracranial calcification is referred to calcification of parenchyma and vascular structures in brain which can be physiologic or pathologic. This study was conducted with the purpose of investigating the frequency, location, pattern, dimensions and estimated volume of intracranial physiologic calcification (IPC) by computer tomography in different age groups. In this cross-sectional retrospective study, brain computed tomography scans of 216 patients were analyzed in 9 age groups each containing 24 patients from 2 to 89 years old. Data were analyzed by SPSS software using one way analysis of variance (ANOVA, post hoc Tukey), chi square, and linear regression tests (P≤0.05 was considered significant). Rate of calcification in different areas were as follows: pineal gland (75.0%), habenula (36.4%), pineohabenula (15.0%), right lateral ventricle choroid plexus (RCP) (67.7%), left lateral ventricle choroid plexus (LCP) (62.7%), falx cerebri (26.8%), petroclinoid ligament (13.2%), tentorium cerebelli (6.8%), third ventricle choroid plexus (0.9%), fourth ventricle choroid plexus (2.7%), basal ganglia (0.9%). A significant correlation exists between the presence of calcification in pineal, habenula, RCP, and LCP (P≤0.001). Nodular shape of calcification was dominant (47.9%). Estimated volume of pineal calcification showed increased levels in group 8 (70–79 years old) compared to group 2 (10–19 years old) (P≤0.05). Since the accurate description of radiologic appearance of IPCs (location, shape, and size) accompanied with age and clinical manifestation is of great importance in diagnosis and distinguishing from pathologic calcification—for example in patients with melatonin dysregulation or schizophrenic patients—this study was required.

Proteome and microbiota analyses characterizing dynamic coral-algae-microbe tripartite interactions under simulated rapid ocean acidification

Ocean acidification (OA) is a pressing issue currently and in the future for coral reefs. The importance of maintenance interactions among partners of the holobiont association in the stress response is well appreciated; however, the candidate molecular and microbial mechanisms that underlie holobiont stress resilience or susceptibility remain unclear. Here, to assess the effects of rapid pH change on coral holobionts at both the protein and microbe levels, combined proteomics and microbiota analyses of the scleractinian coral Galaxea fascicularis exposed to three relevant OA scenarios, including current (pHT = 8.15), preindustrial (pHT = 8.45) and future IPCC-2100 scenarios (pHT = 7.85), were conducted. The results demonstrated that pH changes had no significant effect on the physiological calcification rate of G. fascicularis in a 10-day experiment; however, significant differences were recorded in the proteome and 16S profiling. Proteome variance analysis identified some of the core biological pathways in coral holobionts, including coral host infection and immune defence, and maintaining metabolic compatibility involved in energy homeostasis, nutrient cycling, antibiotic activity and carbon budgets of coral-Symbiodiniaceae interactions were key mechanisms in the early OA stress response. Furthermore, microbiota changes indicate substantial microbial community and functional disturbances in response to OA stress, potentially compromising holobiont health and fitness. Our results may help to elucidate many complex mechanisms to describe scleractinian coral holobiont responses to OA and raise interesting questions for future studies.

Fahr Disease with Seizure as Clinical Manifestation: A Case Series

Brain calcification can occur physiologically and pathologically. Physiological calcification is associated with a degenerative process with globus pallidus as the most common location. Pathological calcifications are associated with several causes such as idiopathic or secondary due to disturbances in mineral metabolism in the body. Fahr disease is a syndrome characterized by calcium and phosphate deposition in several areas, namely the periventricular area, cerebellum and dentate nucleus. Fahr disease is a rare disease with an incidence of <1:100,000 in the general population. In this case report, we describe 2 cases Fahr's disease both in 6th decade of age. Both of these cases present with a clinical manifestation of seizures. The etiology behind the first case is hypoparathyroid post-thyroidectomy while the second case is idiopathic. Imaging showed bilateral calcifications of the basal ganglia and other areas such as the cerebellum and ventricles.

Engineered In vitro Models for Pathological Calcification: Routes Toward Mechanistic Understanding

Physiological calcification plays an essential part in the development of the skeleton and teeth; however, the occurrence of calcification in soft tissues such as the brain, heart, and kidneys associates with health impacts, creating a massive social and economic burden. The current paradigm for pathological calcification focuses on the biological factors responsible for bone‐like mineralization, including osteoblast‐like cells and proteins inducing nucleation and crystal growth. However, the exact mechanism responsible for calcification remains unknown. Toward this goal, this review dissects the current understanding of structure–function relationships and physico‐chemical properties of pathologic calcification from a materials science point of view. We will discuss a range of potential mechanisms of pathological calcification, with the purpose of identifying universal mechanistic pathways that occur across multiple organs/tissues at multiple length scales. The possible effect of extracellular components in signaling and templating mineralization, as well as the role of intrinsically disordered proteins in calcification, is reviewed. The state‐of‐the‐art in vitro models and strategies that can recreate the highly dynamic environment of calcification are identified.

Six months vitamin K treatment does not affect systemic arterial calcification or bone mineral density in diabetes mellitus 2

PurposeVitamin K-dependent proteins are involved in (patho)physiological calcification of the vasculature and the bones. Type 2 diabetes mellitus (DM2) is associated with increased arterial calcification and increased fractures. This study investigates the effect of 6 months vitamin K2 supplementation on systemic arterial calcification and bone mineral density (BMD) in DM2 patients with a history of cardiovascular disease (CVD).MethodsIn this pre-specified, post hoc analysis of a double-blind, randomized, controlled clinical trial, patients with DM2 and CVD were randomized to a daily, oral dose of 360 µg vitamin K2 or placebo for 6 months. CT scans were made at baseline and follow-up. Arterial calcification mass was quantified in several large arterial beds and a total arterial calcification mass score was calculated. BMD was assessed in all non-fractured thoracic and lumbar vertebrae.Results68 participants were randomized, 35 to vitamin K2 (33 completed follow-up) and 33 to placebo (27 completed follow-up). The vitamin K group had higher arterial calcification mass at baseline [median (IQR): 1694 (812–3584) vs 1182 (235–2445)] for the total arterial calcification mass). Six months vitamin K supplementation did not reduce arterial calcification progression (β [95% CI]: − 0.02 [− 0.10; 0.06] for the total arterial calcification mass) or slow BMD decline (β [95% CI]: − 2.06 [− 11.26; 7.30] Hounsfield units for all vertebrae) when compared to placebo.ConclusionSix months vitamin K supplementation did not halt progression of arterial calcification or decline of BMD in patients with DM2 and CVD. Future clinical trials may want to pre-select patients with very low vitamin K status and longer follow-up time might be warranted. This trial was registered at clinicaltrials.gov as NCT02839044

Fahr’s Syndrome and Pseudohypoparathyroidism- A rare clinical entity

Physiological intracranial calcification occurs in about 0.3-1.5% of cases. It is asymptomatic and detected incidentally by neuroimaging. Pathological basal ganglia calcification is due to various causes, such as: metabolic disorders, infectious and genetic diseases. Hypoparathyroidism and pseudohypoparathyroidism are the one of the causes of pathological basal ganglia calcification. Besides tetany and seizures this condition is presented by parkinsonism and dementia. Infections (toxoplasmosis, rubella, cytomegalovirus, cysticercosis, AIDS) give multiple and asymmetric intracranial calcification. Inherited and neurodegenerative diseases cause symmetrical, bilateral basal ganglia calcification which is not related to metabolic disorders. Fahr’ssyndrome is a rare entity characterized by the presence of bilateral intracranial calcifications with predilection for the basal ganglia and dentate nuclei. It is commonly associated with endocrine disorders, particularly parathyroid and Vitamin D disturbances. Herein we report a case of pseudohypoparathyroidism revealed by Fahr’s disease.

Calcifications of the Medial Choroid in the Velum Interpositum: An Unrecognized Site of Physiologic Calcifications Evident on Multidetector Computed Tomography

In adult patients undergoing multidetector computed tomography (CT) of the brain, we observed linear calcification along the deep venous system on thin (<3 mm) sagittal reconstructions. We found no reports of this finding in the velum interpositum (VI) in the imaging literature. We performed a focused examination of the VI on 2 autopsy cases and retrospectively reviewed sagittal, thin-section reconstructions of CT scans of 273 consecutive adult patients. On 2 routine autopsies of the brain, sampling and histologic evaluation was performed of structures within the VI. A series of 273 unselected, sequentially acquired clinical head CT scans of patients ≥60 years old were retrospectively reviewed on a three-dimensional workstation to determine the incidence of this finding and its correlation with patient age. In 1 of the autopsy cases, calcified choroid plexus was identified in the region of the VI; this was also visible on the patient's premorbid CT. In the series of CT scans, linear calcification of ≥9 mm along the deep venous system was evident in 24.5% of cases. The median age of the cases without calcifications was 72 years, while the median age of the cases with calcification was 82; this difference was statistically significant (χ2, P < 0.0005). Evidence supports that linear midline calcification along the internal cerebral veins represents age-related, physiologic calcification of extraventricular choroid plexus within the VI. Awareness of this previously unreported finding on CT will prevent mistaking these physiologic calcifications on CT for evidence of underlying venous pathology. This finding provides additional support that the midline choroid plexus lies within the VI rather than in the third ventricle and expands our understanding of the detailed anatomy of the VI.

Pathological calcification in osteoarthritis: an outcome or a disease initiator?

In the progression of osteoarthritis, pathological calcification in the affected joint is an important feature. The role of these crystallites in the pathogenesis and progression of osteoarthritis is controversial; it remains unclear whether they act as a disease initiator or are present as a result of joint damage. Recent studies reported that the molecular mechanisms regulating physiological calcification of skeletal tissues are similar to those regulating pathological or ectopic calcification of soft tissues. Pathological calcification takes place when the equilibrium is disrupted. Calcium phosphate crystallites are identified in most affected joints and the presence of these crystallites is closely correlated with the extent of joint destruction. These observations suggest that pathological calcification is most likely to be a disease initiator instead of an outcome of osteoarthritis progression. Inhibiting pathological crystallite deposition within joint tissues therefore represents a potential therapeutic target in the management of osteoarthritis.

Evaluation of common findings in brain computerized tomography (CT) scan: A single center study.

BackgroundComputed Tomography (CT) is an invaluable imaging tool in the diagnostic workup of patients presenting with head trauma, stroke, brain tumour and epilepsy. The objective of this study was to document the common intracranial pathologies as revealed by CT in our setting and also determine if the indications for CT scan are justified so that patients are not exposed to radiation unnecessarily.Materials and methodsThis was a cross-sectional study carried out in Hansa Clinic Enugu, Enugu State, Nigeria. Demographic data and brain CT radiological reports with imaging findings and clinical indications for patients referred to this study centre from January, 2017 to January 2019 were retrieved from the CT reports' archives and reviewed retrospectively. Relevant information such age, gender, radiological CT findings and clinical indications were collected using structured proforma.ResultsA total of 300 patients' brain CT radiological reports were included in this study. The mean age of the patients was 41.25 ± 16.5 years with majority been within the age group of 31–40 years 92 (30.67%). Out of 300 cases, normal finding was highest 117 (39%) and the least was intracranial physiological calcification, which is 1 (0.33%). Headache is the most common clinical indication, 53 (17.67%) the least was unsteady Gait, which is 3 (1%). The Chi-square test revealed that there was statistically significance relationship between brain CT findings and clinical indications for the investigations (X2 = 285.60, p = 0.002).ConclusionThe study showed that more males than females undergo brain CT scan with headache being the most common presenting complaint. The majority of findings of the brain CT scans in this study are normal despite, myriads of complaints necessitating the investigations. The study also revealed significant association between clinical indications and CT findings.

Abstract 775: Interaction of Phosphate Transport and Calcification in Placenta Vasculature

Phosphate transport has been associated with pathological vascular calcification, but this relationship remains largely unexplored in placenta tissue. In this study we investigated the interaction of maternal-fetal phosphate transport and placental calcification using in vitro and in vivo models. Sodium-dependent phosphate transporter transcriptomics validated by quantitative RT-PCR revealed that the type III sodium-dependent phosphate transporter family members Slc20a1 and Slc20a2 are the predominant sodium-dependent symporters in both mouse and human placenta. Global loss of Slc20a2 generates multiple maternal and fetal phenotypes. We examined Slc20a2 promoter activity and protein localization of Slc20a2 throughout placentation. Slc20a2 was detected in embryonic structures that give rise to the maternal-fetal interface and in regions of the placenta that are susceptible to vascular calcification in the absence of Slc20a2. Pathologically, vascular malformations were found to precede calcium deposition in the absence of Slc20a2. Activation of osteocalcin in the placenta suggested that physiological calcification mechanisms may potentiate the mineral deposition observed with Slc20a2 loss. Histological analyses of human placenta revealed focal localization of Slc20a2 protein and distinct calcification deposition patterns. Lastly, the BeWo trophoblast model confirmed cellular competency for active, sodium-dependent phosphate symport as well as extracellular matrix calcification. Taken together, our findings support that normal growth and maintenance of the placenta requires Slc20a2. Moving forward, we now propose the working hypothesis that Slc20a2-mediated placental phosphate transport contributes to the energy requirements for rapid placental vascular development, enabling vascular patterning that maximizes surface area and minimizes tissue damage caused by aberrant flow, thereby promoting organ health and transport of nutrients, including phosphorus, across the placenta.

The role of the gasotransmitter hydrogen sulfide in pathological calcification.

Calcification is the deposition of minerals, mainly hydroxyapatite, inside the cell or in the extracellular matrix. Physiological calcification is central for many aspects of development including skeletal and tooth growth; conversely, pathological mineralization occurs in soft tissues and is significantly associated with malfunction and impairment of the tissue where it is located. Various mechanisms have been proposed to explain calcification. However, this research area lacks a more integrative, systemic, and global perspective that could explain both physiological and pathological processes. In this review, we propose such an integrated explanation. Hydrogen sulfide (H2 S) is a newly recognized multifunctional gasotransmitters and tis actions have been studied in different physiological and pathological contexts, but little is known about its potential role on calcification. Interestingly, we found that H2 S promotes calcification under physiological conditions and has an inhibitory effect on pathological processes. This makes H2 S a potential therapy for diseases related to pathological calcification. LINKED ARTICLES: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc.

Arterial tissue transcriptional profiles associate with tissue remodeling and cardiovascular phenotype in children with end-stage kidney disease

Chronic kidney disease (CKD) greatly increases the risk for cardiovascular disease (CVD). However, molecular mechanisms underlying CKD-induced arterial remodeling are largely unknown. We performed a systematic analysis of arterial biopsies from children with stage 5 predialysis CKD participating in the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4 C) study. For comparison, we studied biopsies from children without CKD, coronary bypass vessels from adults with atherosclerotic coronary heart disease without CKD and aortic sections of subtotally nephrectomized rats. In pediatric CKD patients, gene expression was correlated to the cardiovascular phenotype assessed by surrogate end-points. The arterial calcium content correlated with the intima-media thickness (IMT) of biopsied vessels from pediatric CKD patients, was markedly increased compared to biopsies from children without CKD and comparable to adult coronary bypass patients. Significant transcriptional changes included ECM components, pro-calcifying factors, and physiological calcification inhibitors; most were highly accordant with changes observed in adults with atherosclerosis and in uremic rats. Individual gene expression levels were significantly associated with the left ventricular mass index and carotid intima media thickness. Thus, inflammatory processes (TNF, IL-10), calcification inhibitors (CA2), the Wnt-pathway (FGF-2) and foremost, ECM components (HMGA1, VNN1, VCAN), impact pathobiological responses in arteries from children with CKD.

Fahr’s disease

The scientific review based on an analysis of the literature examines key points in the etiology, pathomorphology and clinical picture of basal ganglia calcification. It also involves the so-called physiological calcification of the central nervous system. Juvenile and senile forms of a disease and frequency of occurrence of this nosological form are described. The historical information and modes of inheritance are briefly provided. The article considers the numerous synonyms of this disease and the causes of secondary calcification of the brain (Fahr’s syndrome). Four genes are described associated with primary calcification of the basal ganglia: SLC20A2 and XPR1 coding transmembrane conveyors of inorganic phosphate; PDGFB and PDGFRB which are involved in integrity of a blood-brain barrier and survival of pericytes. Pathogenetic mechanisms of clinical displays of a disease are presented. The article displays the features of macro- and microscopic changes in the brain with this nosology. The characteristic signs of the initial and advanced forms of the disease are described in detail, taking into account the age of the debut of calcification of the basal ganglia. The main and auxiliary instrumental methods for diagnosing this disease are also considered, the results of positron emission tomography and magnetic resonance spectroscopy are described, which confirm the pathophysiological mechanism of neurological manifestations of the disease associated with the disorganization of the front-striatal pathways in the area of ​​calcified basal ganglia. A number of additional general clinical laboratory and functional studies are listed to confirm or exclude the diagnosis of primary family idiopathic ferrocalcinosis (Fahr’s diseases). The main directions in the treatment of the described pathology are given.