Familial Basal Ganglia Calcification Research Articles

SLC20A2-Associated Idiopathic basal ganglia calcification (Fahr disease): a case family report

BackgroundIdiopathic basal ganglia calcification (IBGC) is a genetic disorder of the nervous system commonly known as Fahr disease. IBGC patients with a genetic background are considered to have primary familial brain calcification (PFBC), also known as familial basal ganglia calcification (FBGC), or familial Fahr disease. It is a rare degenerative neurological disorder characterized by extensive bilateral basal ganglia calcification that can lead to a range of extrapyramidal symptoms and neuropsychiatric manifestations. Studies have suggested that more than 50 variants of SLC20A2 gene mutations account for approximately 50% of IBGC cases. There is a wide spectrum of mutation types, including frameshift, nonsense, and splice site mutations in addition to deletion and missense mutations. Here we report a case of familial basal ganglia calcification caused by a frameshift mutation in the SLC20A2 gene. We identified a heterozygous mutation in the SLC20A2 gene, c.1097delG (p.G366fs*89). To our knowledge, this mutation site has not been reported before.Case presentationA 57-year-old male patient was admitted to the hospital with “unstable walking and involuntary movements between the eyes and eyebrows for 6 months”. Based on the patient’s family history, symmetrical calcification foci in the bilateral caudate nucleus head, thalamus, cerebellum and parietal lobe indicated by head CT, and gene test results, the diagnosis of familial Fahr disease caused by mutations in the SLC20A2 gene, c.1097delG p.G366fs*89) was confirmed.ConclusionFor the first time, we identified c.1097delG (p.G366fs*89) as a frameshift mutation in the IBGC family. This frameshift mutation caused the condition in this family of patients. This mutation not only broadens the range of known SLC20A2 mutations but also aids in the genetic diagnosis of IBGC.

'Comment on the Paper "SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia" by Baker et al.'

'Comment on the Paper "SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia" by Baker et al.'

SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia

Idiopathic basal ganglia calcification (IBGC) is characterized by bilateral calcification of the basal ganglia associated with a spectrum of neuropsychiatric and motor syndromes. In this study, we set out to determine the frequency of the recently identified IBGC gene SLC20A2 in 27 IBGC cases from the Mayo Clinic Florida Brain Bank using both Sanger sequencing and TaqMan copy number analysis to cover the complete spectrum of possible mutations. We identified SLC20A2 pathogenic mutations in two of the 27 cases of IBGC (7%). Sequencing analysis identified a p.S113* nonsense mutation in SLC20A2 in one case. TaqMan copy number analysis of SLC20A2 further revealed a genomic deletion in a second case, which was part of a large previously reported Canadian IBGC family with dystonia. Subsequent whole-genome sequencing in this family revealed a 563,256-bp genomic deletion with precise breakpoints on chromosome 8 affecting multiple genes including SLC20A2 and the known dystonia-related gene THAP1. The deletion co-segregated with disease in all family members. The deletion of THAP1 in addition to SLC20A2 in the Canadian IBGC family may contribute to the severe and early onset dystonia in this family. The identification of an SLC20A2 genomic deletion in a familial form of IBGC demonstrates that reduced SLC20A2 in the absence of mutant protein is sufficient to cause neurodegeneration and that previously reported SLC20A2 mutation frequencies may be underestimated.

Pineal Ganglioglioma in a Patient with Familial Basal Ganglia Calcification and Elevated Serum α-Fetoprotein

Pineal ganglioglioma was diagnosed in a 36-year-old man with familial basal ganglia calcification and elevated serum alpha-fetoprotein. The patient was treated surgically with a good result. Only four other cases of this tumor have been reported. His 38-year-old brother also showed basal ganglia calcification and elevated serum chorionic gonadotropin as well as alpha-fetoprotein. Familial basal ganglia calcification with elevated serum alpha-fetoprotein in a nonhepatic benign condition is rare. The pathogenesis of these conditions is discussed.

Pineal Ganglioglioma in a Patient with Familial Basal Ganglia Calcification and Elevated Serum α-Fetoprotein

Pineal Ganglioglioma in a Patient with Familial Basal Ganglia Calcification and Elevated Serum α-Fetoprotein

102 PROGRESSIVE ENCEPHALOPATHY IN PATIENT TREATED WITH PITUITARY HUMAN GROWTH HORMONE

We report the case of a hypopituitary patient treated with human pituitary-derived growth hormone with a neurological disorder initially thought to be Creutzfeld-Jacob disease (CJD). Between 1978. and 1981. he received 150 injections of Kabl-Vitrum Creshormone. In 1985. at the age of 18 he began to have difficulty in speech, writing and balance and exhibited behaviour changes. CT scan of the brain revealed massive calcifications within cerebellar hemispheres. Other laboratory results including cerebrospinal fluid (CSF) analysis, serum electrolytes and parathormone levels and EEG were normal. His father's CT scan of the brain showed a minor calcification of the caudate nucleus, without clinical symptomatology. Follow-up of the patient revealed slow but clear progression of speech, truncal and gait ataxia and coordination difficulties He became withdrawn, depressive and slightly agressiva. Repeated EEGs were normal and the pair of proteins characteristic for CJD were not detected in CSF. Most probably our patient has Fahr's disease (familial basal ganglia calcification) but for a definitive diagnosis histopathology of the brain would be needed.

A survey of 37 cases with basal ganglia calcification (BGC): CT-scan findings of BGC and its relationship to underlying diseases and epilepsy.

Thirty-seven cases that showed bilateral basal ganglia calcification (BGC) were found in 5987 patients. These cases (0.6%) were studied in relation to their CT findings, underlying diseases and epilepsy. CT findings of BGC were divided into "localized" type (33 cases) and "diffuse" type (4 cases). The number of patients with the "localized" type clearly seemed to increase with age. The M:F ratio of the "localized" type was 1:2. The "localized" type was seen in both idiopathic BGC and familial BGC. The "diffuse" type was seen in hypoparathyroidism only. The specific relationship of these two types of BGC to underlying diseases, however, does not fully agree with results so far reported. We experienced a case with familial BGC during this study that appears to be only the 15th so far reported. Partial epilepsy occurred in 75% of epilepsy with BGC, but there seemed to be no direct relationship between BGC and epileptogenicity.

Brain Calcification in Kallman’s Syndrome

We report a 21-year-old white male with Kallman’s syndrome (gonadotropic hypogonadism, hyposmia and sensorineural hearing loss) with extensive brain calcification, demonstrated for the first time by computed tomography. The pattern and anatomic distribution of the extensive brain calcification is nonspecific, being indistinguishable from those seen in other causes of brain calcification (principally diseases related to a disturbance in calcium metabolism), despite the normal serum calcium levels found in this patient. This syndrome, therefore, should be considered along with Cockayne’s, Kearns-Sayre and Down’s syndromes, tuberous sclerosis, carbonic anhydrase II deficiency, congenital mental deficiency and idiopathic familial basal ganglia calcification as another developmental cause of brain calcification, which usually show no disturbance in serum calcium level.

Familial basal ganglia calcification; case diagnosed by displacement of calcification in the basal ganglia.

Bilateral symmetrical calcification in the basal ganglia of the brain is rare. When it occurs, it is most commonly associated with hypoparathyroidism, either idiopathic or following thyroidectomy (2, 3, 9). Less frequently such calcification has been discovered in several members of the same family and their blood relatives, none of whom show evidence of hypoparathyroidism either clinically or by ordinary blood calcium and phosphorus studies (1, 4, 6, 11). The following case summary describes an instance of familial basal ganglia calcification in which routine determinations of blood calcium and phosphorus were within normal limits. A most unusual feature of this case is the unexpected roentgen finding of displacement of the calcified basal ganglia on one side. This permitted the diagnosis of a space-occupying intracranial lesion to be made from examination of the plain films of the skull alone. J. M., a 55-year-old white male, was admitted to the National Hospital, Queen Square, London, under the care of...