Fahr disease

Definition

Fahr disease is a rare, progressive neurological disorder that is often hereditary. Characterized by deposits of calcium in the basal ganglia and other parts of the brain, Fahr disease causes worsening dementia and the loss of routine motor skills, among other symptoms.

Description

Though calcium is important for good health, this mineral can have harmful effects when it appears in parts of the body where it does not belong. In Fahr disease, abnormal deposits of calcium build up in a region of the brain called the basal ganglia (mainly in a section called the globus pallidus), as well as in other parts of the brain. The basal ganglia is the technical name given to clusters of nerve cells that help to initiate and control movements of the body—for example, reaching for a cup of coffee or taking a step forward while walking. The presence of these calcium deposits (referred to as calcifications) interferes with the working of the brain, causing a variety of debilitating mental and physical symptoms that worsen over time. Aside from the basal ganglia, the calcium deposits associated with Fahr disease often appear in other areas of the brain such as the cerebral cortex.

Two important effects of the disease are dementia and the loss of learned motor skills. People affected by Fahr disease may become overly forgetful and easily confused or disoriented. They have trouble performing relatively simple tasks that require basic hand-eye coordination. Most people with the disease experience slurred speech and problems involving involuntary movements or poor coordination. In addition, personality changes and disorders of mood may develop. In one study of 18 people with Fahr disease, half of the participants had symptoms of obsessive-compulsive disorder, major depression , or bipolar disorder . People with Fahr disease may have psychotic symptoms, including hallucinations (visual and auditory), a distorted perception of reality, and paranoid delusions.

As the disease progresses, it causes an increasing degree of paralysis. Muscles become stiff and physical movement is restricted. Aside from these symptoms, people with Fahr disease may experience specific movement disorders: slow, twisting movements of the hands and feet (athetosis) and jerky, rapid movements that resemble spasms (chorea). Vision may also be affected. Because the disease can weaken nerves that carry signals from the eyes to the brain, people with Fahr disease may experience partial or almost complete vision loss. Ear infections have also been reported.

The underlying cause of Fahr disease is unknown. For this reason, it is described as an idiopathic disorder. Fahr disease is often referred to in the medical literature as idiopathic basal ganglia calcification (IBGC). Less common names for the disease include cerebrovascular ferrocalcinosis, non-arteriosclerotic cerebral calcifications, and striopallidodentate calcinosis.

Genetic profile

Fahr disease often runs in families and is believed to be inherited either as a recessive or dominant trait. In the recessive version of Fahr, a person must inherit the same abnormal gene (associated with Fahr) from both parents in order to develop the disease. Therefore, a child who receives only one recessive gene for the disease can become a carrier but will not usually develop symptoms. In the dominant version of Fahr disease, a person may develop the condition after receiving just one copy of the abnormal gene from either the mother or father.

Researchers studying a particular family affected by Fahr disease over several generations discovered a pattern regarding the age at which the condition strikes. The results of this medical study, indicated that each generation with Fahr developed symptoms at an earlier age than previous generations, a phenomenon described as "genetic anticipation." The family (referred to as a "kindred") being analyzed in this study was affected by the dominantly inherited version of the disease.

While studying this kindred, researchers located a gene believed to play a role in the disorder. The gene was named IBGC1 ("IBGC" is short for "idiopathic basal ganglia calcification," another name for Fahr disease). The gene location was identified as 14q, situated on the long arm (called q) of chromosome 14. Despite this finding, more research is necessary to determine the identity and nature of the gene or genes associated with Fahr disease.

Aside from inherited forms, Fahr disease can occur sporadically for reasons that are not well understood. Some medical studies suggest that sporadic cases of Fahr disease may result from an as-yet unidentified infection that affects the fetus in the womb.

Demographics

Fahr disease, which appears to affect men and women equally, can appear at any stage of life, from infancy to adulthood. Some people diagnosed with the disease have no family history of the condition, while in many cases Fahr disease runs in families and affects members of several generations. In people with dominantly inherited Fahr disease, symptoms usually appear anywhere between the ages of 30 and 60. The recessive form of Fahr disease emerges at a younger age, between infancy and young adulthood.

Signs and symptoms

People with Fahr disease have abnormal calcium deposits in the basal ganglia, primarily in the globus pallidus region, and often in other parts of the brain. Loss of brain cells in these areas also occurs. The results of electrocardiogram (ECG) studies, which monitor heartbeats, are often abnormal in people with Fahr disease. Other signs include malfunctioning parathyroid glands and low blood calcium levels.

The disease causes a variety of physical and psychological symptoms. The head of a person with Fahr disease is often smaller and rounder than normal. The condition causes worsening dementia and loss of routine motor skills. Muscle stiffness, movement disorders, and paralysis may occur. Speech often becomes slurred. In some cases, Fahr disease causes vision problems and ear infections. Symptoms of Parkinson's disease may develop as well.

Diagnosis

In simple terms, Fahr disease is diagnosed when calcifications in the basal ganglia are associated with slurred speech, movement disorders, and other specific symptoms. Special imaging procedures such as a CT scan can detect the presence of calcium deposits. Symptoms can be determined by physical and psychological examinations. Friends or family members with relevant observations of the patient's behavior can also be helpful. Blood tests may be recommended to evaluate blood calcium levels and the parathyroid glands. The appearance of Parkinson-like symptoms is not essential to a diagnosis of Fahr disease.

In the absence of other factors, calcium deposits in the basal ganglia do not necessarily indicate the presence of Fahr disease. Such calcifications may be due to a metabolism disorder, infectious disease, or a genetic disorder other than Fahr. In fact, sometimes these calcifications may be present without producing any symptoms or harmful effects, especially in people older than age 60.

Treatment and management

There is no cure for Fahr disease, which worsens over time. The process of calcification cannot be stopped or reversed. Where possible, clinicians focus on alleviating its various mental and physical effects. These may vary to some degree depending on the individual, even among members of the same family. Lithium carbonate, for example, may be recommended to control psychotic symptoms, while antidepressant medications are often used to combat depression. Ear infections associated with Fahr disease can be treated with antibiotics and pain medication.

Prognosis

Due to its damaging effects on the brain and nervous system, Fahr disease is eventually fatal.

Resources

BOOKS

Victor, Maurice, et al. Principles of Neurology. 7th ed. New York: McGraw-Hill, 2001.

PERIODICALS

Geschwind, D. H., et al. "Identification of a Locus on Chromosome 14q for Idiopathic Basal Ganglia Calcification (Fahr Disease)." American Journal of Human Genetics 65 (1999): 764-772.

Lauterbach, E. C., et al. "Neuropsychiatric Correlates and Treatment of Lenticulostriatal Diseases: A Review of the Literature and Overview of Research Opportunities in Huntington's, Wilson's, and Fahr's Diseases. A report of the ANPA Committee on Research. American Neuropsychiatric Association." Journal of Neuropsychiatry and Clinical Neurosciences 10 (1998): 249-66.

Rosenblatt, A., and I. Leroi. "Neuropsychiatry of Huntington's Disease and Other Basal Ganglia Disorders." Psychosomatics 41(2000): 24-30.

ORGANIZATIONS

National Institute of Neurological Disorders and Stroke. 31 Center Drive, MSC 2540, Bldg. 31, Room 8806, Bethesda, MD 20814. (301) 496-5751 or (800) 352-9424. <http://www.ninds.nih.gov>.

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.

WEBSITES

Association of Birth Defect Children, Inc. <http://www.birthdefects.org>.l

Greg Annussek