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Familial Idiopathic Basal Ganglia Calcification

NORD is very grateful to Dr Joao Ricardo Mendes de Oliveira, MD, PhD, Department of Neuropsychiatry, Federal University of Pernambuco, Brazil, for assistance in the preparation of this report.

Synonyms of Familial Idiopathic Basal Ganglia Calcification

  • cerebrovascular ferrocalcinosis
  • Fahr disease, formerly
  • FIBGC
  • striopallidodentate calcinosis

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Familial idiopathic basal ganglia calcification (FIBGC) is a rare neurological disorder characterized by the presence of abnormal calcium deposits (calcifications) of unknown cause. Associated symptoms include progressive deterioration of cognitive abilities (dementia), loss of contact with reality (psychosis), mood swings and loss of acquired motor skills. As the condition progresses, paralysis may develop that is associated with increased muscle stiffness (rigidity) and restricted movements (spastic paralysis). Additional abnormalities may include relatively slow, involuntary, continual writhing movements (athetosis) or chorea, a related condition characterized by irregular, rapid, jerky movements.

Symptoms

Familial idiopathic basal ganglia calcification is characterized by abnormal calcium deposits in the basal ganglia, dentate nucleus, thalami and cerebral white matter of the brain and may be found as early as the first decade of life. Neuropsychiatric symptoms usually begin in the third to fifth decade. Early symptoms may include clumsiness, fatigue, slow or slurred speech and difficulty swallowing (dysphagia). Some individuals with basal ganglia calcification remain free of symptoms for several decades. Progressive deterioration of mental abilities (dementia) and loss of previous motor development are accompanied by spastic paralysis and in some cases, twisting movements of the hands and feet (athetosis). Features of Parkinson disease found in this disorder may include tremors and rigidity, a masklike facial expression, shuffling walk, and a pill rolling motion of the fingers. Muscle cramping (dystonia), uncontrollable spasmodic irregular movements (chorea), and seizures can also occur. Occasional symptoms include sensory changes, headaches and urinary incontinence.

Causes

Familial idiopathic basal ganglia calcification is inherited as an autosomal dominant genetic condition. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. It is not known how many cases of FIBGC are due to a new gene mutation. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.

Wang et al (2012) reported 7 families from China, Spain and Brazil, with different mutations in the SLC20A2 gene on chromosome 8, encoding for a phosphate inorganic transporter (PIT-2). Twin studies suggest that there are inherited patterns of basal ganglia calcification that may be linked to specific genes. Other genes on chromosomes 7, 9 and 14 are also being studied to determine if they are associated with FIBGC.

Affected Populations

The prevalence of FIBGC is unknown. Approximately 30 families have been described with this syndrome.

Related Disorders

Symptoms of the following disorders may be similar to those of familial idiopathic basal ganglia calcification. Comparisons may be useful for a differential diagnosis:

Calcification of the basal ganglia in the brain is found in many medical conditions and can be caused by infections as well as metabolic and genetic syndromes. It is also not uncommon to observe calcium deposits of the basal ganglia in individuals over 60 years of age and this finding is not usually associated with disease

Parkinson disease is a slowly progressive neurologic condition characterized by involuntary trembling (tremor), muscular stiffness or inflexibility (rigidity), slowness of movement and difficulty carrying out voluntary movements. Degenerative changes occur in areas deep within the brain (substantia nigra and other pigmented regions of the brain), causing a decrease in dopamine levels in the brain. Dopamine is a neurotransmitter, which is a chemical that sends a signal in the brain. (For more information on this disorder, choose "Parkinson" as your search term in the Rare Disease Database.)

Hypoparathyroidism is a condition characterized by insufficient production of parathyroid hormones by the parathyroid glands, the small, oval glands located near the thyroid gland in the neck. Parathyroid hormones (along with vitamin D and the hormone calcitonin, which is produced by the thyroid gland) play a role in regulating levels of calcium in the blood. Due to deficiency of parathyroid hormones, affected individuals exhibit abnormally low levels of calcium in the blood (hypocalcemia). Symptoms and findings associated with hypoparathyroidism may include weakness, muscle cramps, excessive nervousness, headaches, and/or increased excitability (hyperexcitability) of nerves resulting in uncontrollable twitching and cramping spasms of certain muscles such as those of the hands, feet, arms, and/or face (tetany). Hypoparathyroidism may result from absence of the parathyroid glands, removal or damage to the parathyroid glands or from several different underlying disorders. In rare cases, hypoparathyroidism may be inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose "hypoparathyroidism" as your search term in the Rare Disease Database.)

Pseudohypoparathyroidism is a hereditary disorder characterized by an inadequate response to the parathyroid hormone, although the hormone is present in normal amounts. This inadequate response affects bone growth and affected individuals may also experience headaches, unusual sensations, weakness, easy fatigue, reduced energy, blurred vision, and/or hypersensitivity to light. Additional symptoms and findings may include stiffness or cramps in the arms and/or legs, palpitations, and/or abdominal pain. In addition, individuals with Pseudohypoparathyroidism may have an abnormally round face, thick short stature, unusually short fourth fingers, and mental retardation. Hormonal and calcium replacement therapy is often helpful, but the lack of growth may persist. (For more information on this disorder, choose "pseudohypoparathyroidism" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
Neuroimaging techniques such as computed tomography (CT) of the brain (the most sensitive technique), magnetic resonance imaging (MRI) and skull X-rays are used to diagnose calcification of the basal ganglia. This finding in combination with a progressive movement disorder, neuropsychiatric problems beginning in the 40’s or 50’s, a lack of biochemical abnormalities or other known causes (infection, toxic exposure, trauma) make the diagnosis very likely.

Treatment
No specific treatment is known for FIBGC. Medications can be used to treat symptoms associated with this condition, such as movement disorders, seizures, anxiety, depression, psychosis and urinary incontinence.

Genetic counseling is recommended for affected individuals and their families, especially for those with mutations at the SLC20A2 gene.

Investigational Therapies

Speech and gait were improved in one patient treated with disodium etidronate, but other neurologic symptoms and calcification were unchanged.

Levodopa therapy was found to be effective in treating parkinsonian features in one individual who had FIBGC and Parkinson disease.

The anticonvulsant oxcarbazepine was effective in treating a Turkish patient with basal ganglia calcification and dyskinesia.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

Contact for additional information about familial idiopathic basal ganglia calcification:

Jo√£o Ricardo Mendes de Oliveira, MD, PhD
Federal University of Pernambuco
Av. Prof. Moraes Rego, 1235
Cidade Universit√°ria, Recife
PE, 50670-901, Brazil
Phone: 55-81-87819856
joao.ricardo@ufpe.br

Organizations related to Familial Idiopathic Basal Ganglia Calcification

References

TEXTBOOKS
Oliveira JRM. Managing Idiopathic Basal Ganglia Calcification ("Fahr's Disease"). New York: Nova Publishing; 2011.

Manyam BV. Fahr Disease. In: The NORD Guide to Rare Disorders. Lippincott, Williams and Wilkins; 2003:532.

JOURNAL ARTICLES
Wang C, Li Y, Shi L, et al. Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet. 2012;44(3):254-256.

Oliveira JR, Lima Filho JL, Zatz M. Identical twins with idiopathic basal ganglia calcification ("Fahr's disease") presenting with a remarkably similar pattern of neuroimaging findings. Parkinsonism Relat Disord. 2009:15:396-397.

Alemdar M, Selek A, Iseri P, et al. Fahr's disease presenting with paroxysmal non-kinesigenic dyskinesia: a case report. Parkinsonism Relat Disord. 2008;14(1):69-71.
Weisman DC, Yaari R, Hansen LA, Thal LJ. Density of the brain, decline of the mind: an atypical case of Fahr disease. Arch Neurol. 2007; 64:756-7.

Baba Y, Broderick DF, Uitti RJ, et al. Heredofamilial brain calcinosis syndrome. Mayo Clin Proc. 2005;80(5):641-51.

Manyam BV. What is and what is not 'Fahr's disease'. Parkinsonism Relat Disord. 2005; 11:73-80.

Modrego PJ, Mojonero J, Serrano M, Fayed N. Fahr's syndrome presenting with pure and progressive presenile dementia. Neurol Sci. 2005; 26:367-9.

Oliveira JR, Spiteri E, Sobrido MJ, et al. Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr disease). Neurology. 2004;63:2165-7.

Oliveira JR, Hopfer S, Papp J, et al. A genome-wide scan for familial idiopathic basal ganglia calcification (Fahr's disease) identifies new candidate regions and confirms genetic heterogeneity. Am J Hum Genet 2003; 73(5):570.

Manyam BV, Walters AS, Keller IA, Ghobrial M. Parkinsonism associated with autosomal dominant bilateral striopallidodentate calcinosis. Parkinsonism Relat Disord. 2001;7:289.

Manyam BV, Walters AS, Narla KR. Bilateral striopallidodentate calcinosis: clinical characteristics of patients seen in a registry. Mov Disord. 2001;16:258-64.

Geschwind DH, Loginov M, Stern JM. Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease). Am J Hum Genet . 1999;65:764-72.

INTERNET
Sobrido MJ, Hopfer S, Geschwind DH. (Updated September 20, 2007). Familial Idiopathic Basal Ganglia Calcification. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1993-2012. Available at http://www.genetests.org. Accessed February 28, 2012.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Basal Ganglia Calcification, Idiopathic,1; IBGC1. Entry No: 213600. Last Edited September 11, 2009. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed February 28, 2012.

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Report last updated: 2012/03/16 00:00:00 GMT+0

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