Fahr Disease: Causes, Symptoms, and Treatment

Introduction:

Fahr disease (FD) is an uncommon disorder occurring due to genetic mutation. Fahr disease is inherited in an autosomal dominant fashion. The condition causes neurodegeneration and abnormal deposition of calcium in the brain. The primary symptoms of Fahr disease are the degradation of motor function, memory loss, seizures, headaches, dysarthria, spasticity, visual impairments, and athetosis. The diagnosis is based on the patient’s medical and family history, along with specific symptoms and specialized laboratory and imaging tests. The treatment mainly comprises drug therapy and physical rehabilitation.

What Is Fahr Disease?

Fahr disease is an uncommon genetic, neurodegenerative condition characterized by unusual calcium deposition in parts of the brain responsible for movement control. These areas may include the basal ganglia and cerebral cortex. The calcium deposit is made up of calcium carbonate and phosphate. In addition to the basal ganglia, abnormal calcium deposits can also be found in the thalamus, hippocampus, dentate nucleus, cerebral cortex, and cerebellar subcortical white matter. The disease was initially described in 1930 by a German neurologist named Karl Theodor Fahr. Fahr disease is a hereditary condition, which means it is genetically passed down from parents to their children. Fahr disease is generally inherited in an autosomal dominant pattern.

What Are the Other Names of Fahr Disease?

Alternate names of Fahr disease are:

• Fahr disease is often referred to as Fahr syndrome in certain cases.

• Bilateral strio-pallido-dentate calcinosis.

• Primary familial brain calcification.

• Calcinosis nucleorum.

What Causes Fahr Disease?

Fahr disease can sometimes be passed on as an autosomal recessive disorder or manifest sporadically; however, it is most frequently reported to be inherited in an autosomal dominant form. Fahr disease's molecular cause has been linked to the following four genes:

• A mutation that causes loss of function in the SLC20A2 (sodium-dependent phosphate transporter 2) gene.

• A variation in the XPR1 (xenotropic and polytropic retrovirus receptor 1) gene. On chromosome 1q, this gene encodes a retroviral receptor with phosphate export function.

• A mutation in the genes PDGFRB (platelet-derived growth factor receptor beta) on chromosome 5q and PDGFB (platelet-derived growth factor subunit B) on chromosome 22q, which code for the receptors for the platelet-derived growth factor family.

Fahr syndrome has a wide range of secondary causes, the most prevalent of which are endocrinopathies, mitochondrial illnesses, and infections.

How Prevalent Is Fahr Disease?

Fahr disease is prevalent in the fifth and sixth decades of life. The majority of patients have good health when they are young and typically get this progressive neurological disease as they get older. The exact prevalence of Fahr disease is unknown due to insufficient investigations and documented cases.

What Are the Symptoms of Fahr Disease?

Signs and symptoms of Fahr disease are as follows:

Movement Disorder Symptoms:

• Parkison’s disease-like symptoms.

• Clumsiness.

• Fatigue.

• Abnormal gait.

• Dystonia.

• Disorientation.

• Slurred speech.

• Muscle cramps.

Paroxysmal choreoathetosis (a movement disorder characterized by sporadic episodes of involuntary movements).

Neuropsychiatric Symptoms:

• Depression.

• Anxiety.

• Dementia.

• Behavioral changes.

• Difficulty in concentrating.

Central Nervous System Symptoms:

• Loss of consciousness.

• Seizures.

• Spasticity (It is a disorder characterized by an unnatural rise in muscular tone or stiffness, which may impair speech or movement and be accompanied by discomfort and pain).

• Impaired speech.

• Tetany (uncontrollable muscular twitches and excessively activated peripheral nerves).

• Vertigo.

• Coma (prolonged period of unconsciousness.

• Headaches.

• Urinary incontinence.

• Impotency.

• Hypertension (increased blood pressure).

How Is Fahr Disease Diagnosed?

Diagnostic criteria for considering a case of Fahr disease:

• Beginning at any age, progressive neurologic dysfunction.

• Basal ganglia and other areas of the brain have bilateral calcification, according to radiographic data.

• The absence of biochemical imbalances is indicative of other underlying systemic illnesses.

• Absence of any kind of infections.

• Family history of Fahr disease.

Further investigations include the following:

• Laboratory Examinations: A patient with Fahr disease has routine lab results within normal ranges. Any abnormality should trigger additional research to rule out any potential secondary etiology of brain calcifications.

• Imaging Tests: Bilateral calcification in several parts of the brain can be seen with the help of imaging tests. A brain CT (computed tomography) scan is the most sensitive technique for locating and determining the extent of calcium deposits. While MRI (magnetic resonance imaging) is less sensitive than a CT scan, it offers better anatomical details. Calcification can also be determined with the help of a plain radiograph of the skull, but this imaging modality is less sensitive as compared to CT scans and MRIs.

• Genetic Testing: The diagnosis of Fahr disease is made in an index patient that satisfies the diagnostic standards.

How Is Fahr Disease Treated?

As with other neurodegenerative conditions, there is currently no known cure for Fahr disease; thus, symptomatic relief is the main focus of treatment.

Symptomatic treatment includes the following:

• Management of seizure with the help of anti-epileptic drugs.

• Pain medications for chronic headaches.

• Urinary incontinence can be treated with anticholinergic drugs.

• Drugs for management of depression, anxiety, etc., associated with Fahr disease.

• Movement disorders can be managed with the help of neuroleptics.

Drug Cautions: Patients with Fahr disease who take Carbamazepine, Benzipenes, or Barbiturates may experience more gait dysfunction. Antidepressants and anxiolytics should be used with extreme caution by psychiatric and neurological patients since Fahr disease patients have a low threshold for adverse effects. Lithium has been shown to increase a patient’s risk of seizures, and extrapyramidal symptoms can worsen while using neuroleptics.

Physical Rehabilitation:

• Exercises that maintain range of motion and avoid contractures include passive stretching and assisted stretching.

• Strengthening of underutilized muscles.

• Improving posture stability.

• Methods to improve gait dysfunction.

• Deep brain stimulation for hyperkinetic diseases, soft tissue release for spasticity, relaxation treatments for anxiety, or sensory stimulation for basal ganglia dysfunction.

What Are the Complications of Fahr Disease?

Complications of Fahr disease are as follows:

• Depression.

• Dementia.

• Psychosis.

• Difficulty in sleeping.

• Epilepsy.

• Muscle contractions.

• Frequent falls.

• Orthopedic complications.

Conclusion:

Fahr disease is a rare condition. Patients with Fahr disease have an unexpected and variable prognosis. The severity of the disease is not correlated with the age of disease commencement, the presence of symptoms, or the degree of brain calcifications. About 95 % of the cases manifest by the age of 50. There is no definitive cure for the disease, and the treatment is primarily based on symptomatic relief.