特発性基底核石灰化症

Bilateral symmetrical calcification of striatum and pallidum with or without involvement of other brain structures is a rare radiological finding. Genetic causes predominates once hypoparathyroidism is ruled out. Clinical features include a variable combination of neuropsychiatric and motor symptoms, including dystonia, Parkinsonism, ataxia, psychosis, dementia, chorea, and frontal-subcortical cognitive dysfunction. One third of primary familial brain calcification is asymptomatic. Solute carrier 20 A2 gene mutation accounts for the majority of primary familial brain calcification. Here we describe a case of primary brain calcification due to a novel mutation in Solute carrier 20A gene in a 55-year-old woman.

BACKGROUND: Fahr's syndrome, sometimes referred to as primary familial brain calcification, is an uncommon neurodegenerative disease that is typified by bilateral, symmetrical intracranial calcifications that primarily affect the cerebral cortex, thalamus, dentate nuclei, and basal ganglia. The condition is often associated with movement disorders, seizures, neuropsychiatric symptoms, and cognitive decline. However, it can sometimes go unnoticed and be discovered by accident when imaging for unrelated conditions. Early symptoms can be detected in non-neurological settings, even though neurologists deal with them most of the time. This highlights the importance of interdisciplinary vigilance in healthcare. Dental professionals, particularly prosthodontists, may occasionally experience systemic manifestations during routine diagnostic evaluations, emphasizing the need for a comprehensive clinical approach, including movement disorders and neuropsychiatric conditions. CASE: A 39-year-old woman presented at the prosthodontics department of KGMU, complaining of difficulty chewing food due to missing posterior teeth. Her medical history included longstanding bilateral sensorineural hearing loss and epilepsy managed with antiepileptic medications for over 12 years. The results of a routine pre-prosthetic evaluation, which included panoramic radiography, raised the possibility of abnormal intracranial calcification. Additional evaluation using cranial computed tomography (CT) confirmed bilateral, symmetrical calcifications in the thalamus, subcortical white matter, and basal ganglia that resembled Fahr's syndrome. The patient was referred to the Department of Neurology for further assessment. In order to rule out secondary causes of calcification, other biochemical tests, such as serum calcium level, phosphate, parathyroid hormone, and vitamin D levels, were all within normal ranges. It was determined that idiopathic Fahr's syndrome was the cause. Since the condition is progressive, the patient was recommended to have frequent follow-ups even though there were no additional neurological symptoms. Potential neurological effects were closely monitored during the dental rehabilitation process. CONCLUSION: In this case, Fahr's syndrome was accidentally discovered. This case underlines the importance of vigilance in dental practice, where incidental findings may lead to early diagnosis of systemic neurological conditions such as Fahr's syndrome.

XPR1 encodes the only known phosphate exporter in human cells and regulates the export of inorganic phosphate (Pi). To date, heterozygous pathogenic variants have been reported to be associated with autosomal-dominant idiopathic basal ganglia calcification-6 (IBGC6; MIM: 616413). We collate clinical information on individuals with biallelic XPR1 variants and use in silico and cell-based studies to evaluate pathogenicity. Four consanguineous families have been documented, with a severe neonatal phenotype presenting with persistent pulmonary hypertension, chronic lung disease, cardiomyopathy, and hypophosphatemia. Affected individuals exhibit microcephaly, intracranial calcifications, and profound neurodevelopmental impairment; the prognosis is generally poor. Exome and Sanger sequencing confirmed segregation with homozygosity for a rare, likely deleterious, biallelic XPR1 variant NM_004736.4: c.1811G>A: p.Arg604Gln. Analysis of primary cell lines showed stable expression of the XPR1 protein. In silico structural analysis supported the variant's deleterious nature. Published mutagenesis studies demonstrate that mutations at the arginine residue (Arg604) within the second putative Pi coordination site substantially impair Pi export in functional flux assays. This study establishes a link between a novel severe neonatal disease and specific biallelic variants in XPR1 that result in a loss-of-function phenotype.