Familial Idiopathic Basal Ganglia Calcifications

Familial Idiopathic Basal Ganglia CalcificationsFamilial Idiopathic Basal Ganglia Calcifications (FIBGC, Fahr’s disease, Bilateral striopallidodentate calcinosis, Cerebrovascular ferrocalcinosis) is a rare neurodegenerative disease characterized by the bilateral symmetrical calcification of the basal ganglia.

The disorder is known to have affected about 60 families, although it is supposed to be underdiagnosed. Such patients are often misdiagnosed as having schizophrenia, dementia, or Parkinson’s disease. Calcium deposits appear in the basal ganglia, brain cortex, dentate nucleus and thalamus. Except the familial cases of Fahr’s disease non-familial cases were reported.

Causes


FIBGC is inherited in an autosomal dominant pattern. The mutations are found in SLC20A2 or PDGFRB gene. Other cases of FIBGC are associated with changes in chromosomes 2, 7, 9, and 14, although specific genes are not known.

The SLC20A2 (solute carrier family 20 member 2) gene regulates the synthesis a protein called sodium-dependent phosphate transporter 2 (PiT-2). This protein plays is  needed to maintain  phosphate homeostasis (regulating phosphate levels within the body) by transporting phosphate across cell membranes. The SLC20A2 gene mutations in FIBGC lead to the production of a PiT-2 protein that cannot effectively transport phosphate into cells. Phosphate levels in the bloodstream increases. In the brain, the excess phosphate combines with calcium and forms deposits.
The PDGFRB (platelet derived growth factor receptor beta) gene regulates production of  a protein that plays a role in activating signaling pathways that control many cell processes, although it is unclear how these mutations cause FIBGC. Probably occurs alteration of signaling within cells that line blood vessels in the brain, causing them to take excessive amount of calcium. Alternatively, changes in the PDGFRB protein could disturb phosphate transport signaling pathways, causing an increase in phosphate levels and the formation of calcium deposits.

It is suggested that calcium deposits lead to the characteristic features of FIBGC by interrupting signaling pathways in various parts of the brain. The most charecterisctic features of the disease are caused by the disturbed connection between the basal ganglia and the frontal lobes, which regulate the behavior and motivation of the humans.

The most commonly affected region of the brain is the lenticular nucleus and the internal globus pallidus. Calcifications in the caudate, dentate nuclei, putamen and thalami are also typical. The calcium deposites are also found in thalamus, centrum semi-ovale, cerebellum and cerebral white matter.

[See also: Menkes disease]


Risk factors


The familial history of familial Idiopathic Basal Ganglia Calcifications or at least one of parents is affected the offspring is at risk and genetic counseling is recommended.

Symptoms of Familial Idiopathic Basal Ganglia Calcifications 

The symptoms of FIBGC include motor, psychiatric and behavioral disturbances. The signs appear usually in adulthood. The manifestation of FIBGC comprises clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping. Often the patients develop migraine and seizures.
Psychiatric features of the disorder are: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, catatonia, schizophrenia-like psychosis, aggression, irritability and personality change. Other clinical features include: Parkinsonism, syncope, orthostatic hypotension, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis.
The severity of the disorder varies from person to person. While some persons seem to present to symptoms of the disease, the others develop significant motor and psychiatric problems.

 

Diagnosis


To verify the diagnosis neuroimaging (CT, MRI, plain skull radiography) is required: the bilateral calcification of the basal ganglia can be seen. At the same time it is vital to exclude any metabolic, infectious, toxic, or traumatic cause. The familial history of the disorder and genetic testing will help identify the disease.

 

Treatment


There is no specific treatment of the FIBGC. Usually the treatment includes symptomatic treatment. Anticholinergics are used to reveal the urinary incontinence, appropriate antiepileptic drugs (AEDs) are needed for seizures. To reduce the psychotic symptoms haloperidol or lithium carbonate can be used.
But there is no way known to avoid the disorder from the progression.

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