The Pathology of Primary Familial Brain Calcification: Implications for Treatment

Xu, Xuan; Sun, Hao; Luo, Junyu; Cheng, Xuewen; Lv, Wenqi; Luo, Wei; Chen, Wan‐Jin; Xiong, Zhi‐Qi; Liu, Jing-Yu

doi:10.1007/s12264-022-00980-0

Cited by 18 publications

(19 citation statements)

References 166 publications

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“…Nimodipine, a calcium channel blocker in the CNS, has been unsuccessfully tried to attenuate PFBC symptoms [ 52 ]. Bisphosphonates, commonly used for the treatment of osteoporosis, have been reported to improve symptoms in single cases, without a demonstrated reduction in calcium deposition on CT scans [ 53 ]. In a series of seven patients, Oliveira et al observed stabilization of disease progression after administering alendronate without significant side effects, but no changes on brain calcium deposition were observed and no control group was used for comparison [ 54 ].…”

Section: Clinical Managementmentioning

confidence: 99%

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The clinical and genetic spectrum of primary familial brain calcification

2023

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Primary familial brain calcification (PFBC), formerly known as Fahr’s disease, is a rare neurodegenerative disease characterized by bilateral progressive calcification of the microvessels of the basal ganglia and other cerebral and cerebellar structures. PFBC is thought to be due to an altered function of the Neurovascular Unit (NVU), where abnormal calcium-phosphorus metabolism, functional and microanatomical alterations of pericytes and mitochondrial alterations cause a dysfunction of the blood–brain barrier (BBB) and the generation of an osteogenic environment with surrounding astrocyte activation and progressive neurodegeneration. Seven causative genes have been discovered so far, of which four with dominant (SLC20A2, PDGFB, PDGFRB, XPR1) and three with recessive inheritance (MYORG, JAM2, CMPK2). Clinical presentation ranges from asymptomatic subjects to movement disorders, cognitive decline and psychiatric disturbances alone or in various combinations. Radiological patterns of calcium deposition are similar in all known genetic forms, but central pontine calcification and cerebellar atrophy are highly suggestive of MYORG mutations and extensive cortical calcification has been associated with JAM2 mutations. Currently, no disease-modifying drugs or calcium-chelating agents are available and only symptomatic treatments can be offered.

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Section: Clinical Managementmentioning

confidence: 99%

“…At present, treatment of PFBC-related symptoms remains symptomatic. Antipsychotics and antidepressants are used for neuropsychiatric disturbances [ 53 ]. In patients with parkinsonism, L-Dopa has been used with variable response.…”

Section: Clinical Managementmentioning

confidence: 99%

The clinical and genetic spectrum of primary familial brain calcification

2023

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“…The insertion c.348_c.349insCTGGCCTTCCGC variant is a known pathogenic mutation ( 8 ). However, the loss-of-function c.580G > T MYORG gene variant has not been reported in ClinVar, and no publication has reported this mutation so far ( 1 – 3 , 8 , 11 ). Both variants were predicted to be damaging by multiple in silico prediction tools, including SIFT, Polyphen2, CADD, and MutationTaster.…”

Section: Case Presentationmentioning

confidence: 99%

A novel MYORG mutation causes primary familial brain calcification with migraine: Case report and literature review

Song

Zhao

Wen³

et al. 2023

Front. Neurol.

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Primary familial brain calcification (PFBC) is a disorder in which pathologic calcification of the basal ganglia, cerebellum, or other brain regions with bilateral symmetry occurs. Common clinical symptoms include dysarthria, cerebellar symptoms, motor deficits, and cognitive impairment. Genetic factors are an important cause of the disease; however autosomal recessive (AR) inheritance is rare. In 2018, the myogenesis-regulated glycosidase (MYORG) gene was the first to be associated with AR-PFBC. The present case is a 24-year-old woman with AR-PFBC that presented with migraine at the age of 16 years. Symmetrical patchy calcifications were seen in the bilateral cerebellopontine nuclei, thalamus, basal ganglia, and radiocoronal area on computed tomography and magnetic resonance imaging. AR-PFBC with migraine as the main clinical symptom is rare. Whole-exome sequencing revealed a compound heterozygous mutation in the MYORG gene, one of which has not been previously reported. Our case highlights the pathogenic profile of the MYORG gene, and demonstrates the need for exclusion of calcium deposits in the brain for migraine patients with AR inheritance.

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“…SLC53A1 (xenotropic and polytropic retrovirus receptor 1, XPR1) is thought to be a Pi exporter and is ubiquitously expressed. Several studies have reported a correlation between altered XPR1 expression/function and placental calcification, familial brain calcification, and Fanconi syndrome [16][17][18][19][20][21]. However, how XPR1 is also involved in regulating Pi metabolism in cells and the body is unclear.…”

Section: Phosphate Transporter Classification In the Bodymentioning

confidence: 99%

Regulation of Phosphate Transporters and Novel Regulator of Phosphate Metabolism

Koike,

Uga,

Shiozaki

et al. 2023

Endocrines

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Phosphorus is essential for all living organisms. It plays an important role in maintaining biological functions, such as energy metabolism, cell membrane formation, and bone mineralization. Various factors in the intestine, kidneys, and bones regulate the homeostasis of the inorganic phosphate (Pi) concentration in the body. X-linked hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets, is characterized by an impaired mineralization of the bone matrix, hypertrophic chondrocytes with hypophosphatemia, and active vitamin D resistance in childhood. Phosphate-regulating gene with homologies to endopeptidases on the X chromosome was recognized as the responsible gene for XLH. XLH is classified as fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets. The enhanced FGF23 stimulates renal phosphate wasting by downregulating sodium-dependent Pi cotransporters, NaPi2a and NaPi2c proteins, in the proximal tubules. Recently, transmembrane protein (Tmem) 174 has been identified as a novel regulator of phosphate transporters. This review introduces the role of Tmem174 in the Pi homeostasis in the body.

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The Pathology of Primary Familial Brain Calcification: Implications for Treatment

Cited by 18 publications

References 166 publications

The clinical and genetic spectrum of primary familial brain calcification

The clinical and genetic spectrum of primary familial brain calcification

A novel MYORG mutation causes primary familial brain calcification with migraine: Case report and literature review

Regulation of Phosphate Transporters and Novel Regulator of Phosphate Metabolism

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