A Japanese family with idiopathic basal ganglia calcification with novel SLC20A2 mutation presenting with late-onset hallucination and delusion

OBJECTIVE: To describe a Japanese family with idiopathic basal ganglia calcification (IBGC) with novel SLC20A2 mutation presenting with late-onset hallucination and delusion. BACKGROUND: IBGC, also known as Fahr disease, is a neuropsychiatric disorder characterized by symmetric calcification in the basal ganglia and other regions in central nervous system without apparent metabolic disorders. Clinical features include a variable combination of movement disorders and neuropsychiatric symptoms. Recently, SLC20A2 mutations have been identified in several IBGC families with autosomal dominant inheritance. DESIGN/METHODS: Case: A 73-year-old Japanese woman developed an auditory hallucination and delusion. Neuropsychological tests revealed that she had short-term memory loss, working memory deficit, and impaired cognitive flexibility. Her brain CT images revealed symmetric calcification in the basal ganglia, thalamus, subcortical white matter, and cerebellar dentate nuclei. Her elder sister aged 80 years and her brother aged 78 were also examined. Although both of them were asymptomatic, brain CT images revealed that her brother had calcification in similar regions with higher severity than the patient. RESULTS: We found the novel SLC20A2 missense mutation of p.L108P both in the patient and her asymptomatic brother with brain calcification. The missense mutation of p.L108P was predicted as probably damaging by PolyPhen-2 and deleterious by SIFT. Leucine at position 108 is well conserved among species. The missense mutation causes an amino acid substitution located in ProDom domain of SLC20A2, which is critical for Pi transport function. This mutation was absent in her asymptomatic sister without brain calcification and 196 unrelated Japanese controls. 99 mTc-ECD single-photon emission CT revealed hypoperfusion at the ventrolateral prefrontal cortex of the proband. CONCLUSIONS: We identified the first case of genetically proven IBGC in a Japanese family with a SLC20A2 mutation. Our case may emphasize the importance of evaluating calcification by brain CT in elderly patients with hallucination and delusion. Disclosure: Dr. Kasuga has nothing to disclose. Dr. Konno has nothing to disclose. Dr. Nishizawa has nothing to disclose. Dr. Ikeuchi has nothing to disclose.