SLC20A2-related primary familial brain calcification with purely acute psychiatric symptoms: a case report

Abstract

Background Primary familial brain calcification (PFBC) is a rare inherited neurological disorder characterized by bilateral basal ganglia calcification with a series of motor and nonmotor symptoms. Mutations in the SLC20A2 gene, encoding the PiT2 protein, are the major cause of the disease. Here, we report a Chinese PFBC family carrying a SLC20A2 gene mutation, and the proband presented with purely acute psychiatric symptoms, which has been rarely reported in this disease. Case presentation A 38-year-old woman was hospitalized due to disorganized speech; disordered thought contents; disorganized behaviour; emotional instability and lability; and grandiose words, actions and facial expressions. Brain computerized tomography (CT) revealed calcification in the basal ganglia; cerebellar dentate nuclei; and subcortical, periventricular, and deep white matter regions in she and her family members. Through mutation analysis, a heterozygous truncating mutation, c.1723G > T, p.(Glu575*), was identified in the SLC20A2 gene in this family. Thus, this patient was diagnosed with genetically confirmed PFBC, and she responded well to a low dose of antipsychotic drugs. The penetrance of the disease in this family was only 33%, which was significantly lower than that in most families carrying SLC20A2 gene mutations. Conclusions Patients with SLC20A2-related PFBC might present with psychiatric symptoms alone, and the penetrance of the disease may be quite low, which adds to the clinical heterogeneity of the disease.

The Genetics of Primary Familial Brain Calcification: A Literature Review

“…SLC20A2 is the most common PFBC gene; heterozygous variants have been identified in more than 60% of genetically confirmed PFBC patients [ 3 ]. A missense change is the most common variant type, followed by frameshift, nonsense, and splice site variations, without obvious hotspots for pathogenic variants ( Figure 1 a) [ 3 , 6 , 7 , 17 , 18 , 21 , 23 , 37 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ]. Functionally, both haploinsufficiency and dominant negative effects have been described; the loss of normal PiT2 function results in extracellular Pi accumulation and subsequent calcium phosphate formation [ 6 , 42 ].…”

Brain Calcifications: Genetic, Molecular, and Clinical Aspects

“…Of note, pontine calcifications are typically overserved in subjects with mutations or MYORG [62]. In subjects with PFBC, serum levels of calcium, parathormone (PRH), and vitamin D were found to be within range [26,41,42,50,51,55,57,[63][64][65][66][67].…”

Small vessel disease in primary familial brain calcification with novel truncating PDGFB variants

“…Currently, pathogenic variants in SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, JAM2, and CMPK2 are known to be genetic causes of PFBC [5]. White matter hyperintensities, presumably of vascular origin, have previously been described in PFBC patients with SLC20A2 [6], PDGFRB [7] and PDGFB [8][9][10] variants, and have been explained by the impairment of pericyte recruitment during angiogenesis leading to vascular dysfunction [8,11]. One previous study has reported alterations in the architecture of extracerebral blood vessels of one patient with PFBC and a pathogenic PDGFB variant [8].…”