Primary Familial Brain Calcification With <i>XPR1</i> Mutation Presenting With Cognitive Dysfunction

Dear Editor,Basal ganglia calcification is a common incidental finding in brain imaging, being reported in 20%-30% of the elderly. 1 More than 50 clinical diagnoses have been reported to be associated with calcium accumulation in the basal ganglia. 2 This condition was previously called familial idiopathic basal ganglia calcification, Fahr syndrome, Fahr's disease, and striopallidodentate calcinosis, but primary familial brain calcification (PFBC) was coined to imply that there is a genetic component.Seven Mendelian genes (SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, JAM2, and CMPK2) for PFBC have been discovered. 3Here we report the first Korean case of PFBC caused by an XPR1 mutation, who presented with early-onset cognitive decline with apathy and mild parkinsonism.A 54-year-old female presented with a 3-year history of cognitive deficit.She complained of difficulty in pronouncing words, comprehending complex sentences, and mathematical calculations, which had progressed over the previous year.She exhibited apathy, depression, anxiety, sleep disturbance, and nocturia.She has been taking medications for hypertension, type-2 diabetes mellitus, and dyslipidemia.There was no family history of any neurological disorders.A neurological examination revealed a moderate degree of dysarthria, mild symmetric bradykinesia, and rigidity in both upper extremities.Her gait and postural stability were intact.She has scores of 10, 17, and 15 on the Unified Parkinson's Disease Rating Scale part III score, Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment Test (MoCA), respectively.A comprehensive neuropsychological study using the Seoul Neuropsychological Screening Battery revealed mild cognitive impairment involving multiple cognitive domains including memory, attention, language, and visuospatial function.Her score on the Korean version of the Short Form of the Geriatric Depression Scale (SGDS-K) was 9, suggesting mild depression.Her score on the Withdrawal/Apathy/Lack of Vigor (WAV) subscale was 3/3.Laboratory studies revealed normal levels of serum calcium, inorganic phosphorous, 25-hydroxy vitamin D, osteocalcin, and parathyroid hormone.Low-dose methimazole was started since a thyroid function test indicated subclinical hypothyroidism.Other routine blood test results were normal.Computed tomography (Fig. 1A-C) and magnetic resonance imaging (MRI) (Fig. 1E-H) revealed dense calcifications in both corona radiata, the basal ganglia (especially the globus pallidus), and the dentate nucleus of the cerebellum. 18F-FP-CIT [(3-[ 18 F]fluoropropyl)-2carbon ethoxy-3-(4-iodophenyl) nortropane] positron-emission tomography (PET) showed preserved dopamine transporter (DAT) binding (Fig. 1D).Fluorodeoxyglucose (FDG) PET showed diffusely decreased FDG uptake in the frontal and parietal lobes and the cerebellum, while showing relatively preserved uptake in the sensorimotor cortex and basal ganglia (Fig. 1I-L).Screening for mutations by whole-exome sequencing revealed the heterozygous missense mutation c.1871G>A (p.Arg624His, NM_004736.

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