More than meets the eye: Searching for additional findings in primary brain calcification

• Published in: Journal of the neurological sciences 2017-08, Vol.379, p.117-118
• Main Authors: Ferreira, Laura Durão, Borges-Medeiros, Rayssa L, de Oliveira, João Ricardo M
• Format: Article
• Language: English
• Subjects: Cerebrospinal fluid; Neurology; PFBC; White matter hyperintensities
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2017.05.058

Highlights • Primary familial brain calcification (PFBC) has diverse presentations • Impairment beyond the brain has been described in PFBC patients • Findings emphasized here include elevated CSF-Pi and white matter hyperintensities • Such alternative medical findings appear as potential biomarkers for PFBC diagnosis • Combined, study findings reinforce the necessity of further systemic studies on PFBC MANUSCRIPT. Dear Editor, Recent studies regarding primary familial brain calcification (PFBC) indicate that there is more to this disease than just progressive calcifications in the basal ganglia, thalamus and dentate nuclei [1] . Alternative imaging findings such as white matter hyperintensities (WMH), biochemical imbalances represented by elevated inorganic phosphate levels in the cerebrospinal fluid (CSF-Pi), and damage of microvessels in tissues other than the brain are some of the evidences showing that brain calcifications might not be the only thing to look at [2–6] . An example of this is shown in the letter from Paucar and colleagues published in this same journal in February 2017 [2]. The authors report a c.1399C > T (R467X) variation in exon 8 of the SLC20A2 gene in a 54 year-old woman with elevated CSF-Pi and WMH. They described neuropsychiatric manifestations related to PFBC, besides a medical history of type 1 diabetes mellitus (T1DM), hypertension, obstructive sleep apnea and cataracts. Their preliminary CSF analysis suggests that the integrity of the blood brain barrier (BBB) was maintained [2]. In support of the work above, Jensen et al. (2016) [3] and Wallingford et al. (2016) [4] also reported markedly elevated phosphate levels in the CSF of Slc20a2 knockout (KO) mice in the presence of an intact BBB. Curiously, additional phenotyping of these same mice shows other findings such as decreased body length and weight, abnormal lens and iris morphology with cataract, and various abnormalities in bone structure and composition [7] . Furthermore, it was noted that Slc20a2 KO mice exhibited unbalanced fat to lean mass ratio, decreased fasted circulating glucose level, increased circulating alkaline phosphatase level and increased circulating magnesium level [7] . Finally, calcification on the eyes and optic nerve in Slc20a2 KO mice was also reported by Wallingford et al. (2016) [4]. Further findings in skin and hair have also been described in PFBC patients. Microcalcifications in small vessels, pericytes and thickening of the basal membrane hav