What is Primary Familial Brain Calcification?
Primary familial brain calcification (PFBC) is a genetic disorder in which abnormal calcium deposits (calcification) accumulate in blood vessels in the brain. The calcification usually affects the basal ganglia, the part of the brain that controls movement. However, other parts of the brain may be affected as well.
The disorder is also sometimes called Fahr’s disease.
Symptoms of PFBC
The most common symptoms of PFBC are those related to movement, but up to a third of people with the disorder also experience psychiatric symptoms. Common symptoms of PFBC include:
- Slow movements
- Rigid muscles
- Muscle tremors
- Walking difficulties
- Involuntary muscle movements or tensing
- Difficulty swallowing
- Speech impairment
- Memory loss
- Concentration problems
- Bladder control problems
- Disconnection from reality (psychosis)
What Causes Primary Familial Brain Calcification?
PFBC is caused by abnormal changes (mutations) in one of several different genes. Most commonly, the affected gene is SLC20A2, a gene that carries instructions for making a protein vital in the transport of phosphate into brain cells. The mutation leads to elevated phosphate levels in the bloodstream, which, in turn, promotes calcium deposits inside the cells.
The disorder may be caused by mutations in other genes, including PDGFRB, although it is unclear how these mutations cause calcification. There is no known genetic mutation in about half of PFBC cases, but scientists believe these cases are caused by mutations that haven’t yet been identified.
Is Primary Familial Brain Calcification Hereditary?
Most of the time, PFBC is inherited in an autosomal dominant pattern, meaning that children may develop the disorder if they inherit even one copy of the mutated gene from either of their parents. If a parent carries the disorder-causing mutation, they will have a 50 percent chance of having an affected child with each pregnancy. A person with PFBC usually has at least one parent who also has the disorder.
In a smaller number of cases, PFBC is inherited in an autosomal recessive pattern. This means that a child must inherit two copies of the gene mutation, one from each parent, to develop the disorder. People who have only one copy of the mutated gene will not develop PFBC but will be carriers who can pass the mutation on to their children. Two carrier parents have a 25 percent chance of having a child with PFBC with each pregnancy. Half of their pregnancies will produce a carrier, and a quarter of the pregnancies will produce a child with no mutated genes.
How Is Primary Familial Brain Calcification Detected?
Symptoms of PFBC usually begin in adulthood, in a person’s 30s or 40s, but they can emerge at any stage of life. Early signs may vary according to the age of onset. Onset in childhood often begins with motor and mental developmental delays. Young-adult onset is commonly associated with psychiatric symptoms. Late-onset (after age 50) is more often associated with dementia and movement disorders.
Common early signs of PFBC include:
- Walking difficulties
- Speech problems
- Swallowing difficulties
How Is Primary Familial Brain Calcification Diagnosed?
A doctor may suspect PFBC if a patient exhibits neurological symptoms and has a family history of the disorder. The diagnostic process will aim to rule out other possible causes for the symptoms and look for the characteristic signs of PFBC. Diagnostic steps may include:
- Physical and neurological exams
- Laboratory tests to rule out other causes, including infections, metabolic disorders, or exposure to toxins.
- Magnetic resonance imaging (MRI) or other imaging scans to detect the pattern of brain degeneration characteristic of FFI.
- Genetic testing to look for gene mutations associated with PFBC.
PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.
How Is Primary Familial Brain Calcification Treated?
PFBC has no cure, and no treatment will halt or reverse the progression of its symptoms. Treatment options focus on managing symptoms and preventing complications. Possible treatments include:
- Anticonvulsant medications to control seizures
- Antidepressants or other medications to treat psychiatric symptoms such as anxiety, depression, or obsessive-compulsive disorder (OCD)
- Medication to treat bladder-control problems
- Regular monitoring of neurological and mental health symptoms
How Does Primary Familial Brain Calcification Progress?
In many cases, PFBC causes no symptoms, and the disorder is only discovered incidentally during brain-imaging scans conducted for another reason. However, in symptomatic patients, movement-related and psychiatric symptoms usually worsen over time. Severe cases can lead to significant disabilities and a shortened life expectancy.
How Is Primary Familial Brain Calcification Prevented?
There is no known way to prevent PFBC. However, a genetic counselor can advise people with a family history of PFBC about their risk if they plan to have children.
Primary Familial Brain Calcification Caregiver Tips
- Educate yourself about the disorder, its effects, and the side effects of medications used to treat it. PFBC patients are at higher risk of developing depression and anxiety. Be on the lookout for the warning signs of these conditions.
- Join a support group for caregivers. Caregivers are at risk of developing physical and mental health issues, too. So take time for yourself, and get the help you need when you feel overwhelmed.
Primary Familial Brain Calcification Brain Science
The involvement of the basal ganglia in PFBC helps to explain the disorder’s movement-related symptoms. The basal ganglia are structures deep within the brain that primarily control motor functions, and problems with these structures are associated with movement disorders such as Parkinson’s disease.
It is less apparent how calcification in the basal ganglia produces the neuropsychiatric symptoms commonly associated with PFBC. However, some scientists believe that calcium deposits impair communication between the basal ganglia and other parts of the brain, especially the frontal lobes. These brain structures are vital in functions such as problem-solving, reasoning, and judgment. Thus, impaired function of the frontal lobes, as well as other parts of the brain that regulate mood and social behavior, could be responsible for PFBC’s psychiatric symptoms.
Primary Familial Brain Calcification Research
Title: Cortical-Basal Ganglia Speech Networks
Principal Investigator: Robert M Richardson, MD, PhD
Massachusetts General Hospital
In this study, researchers want to learn more about brain activity related to speech perception and production.
Speech production is disrupted in a number of neurological diseases that involve the basal ganglia, including Parkinson’s disease (PD) and dystonia. The investigators will use a novel experimental approach and combination of analytic techniques to elucidate the contribution of neural activity in cortical-basal ganglia circuits to the hierarchical control of speech production in subjects undergoing deep brain stimulation surgery.
Title: Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism
Stage: Not Yet Recruiting
Principal investigator: Khashayar Dashtipour, MD, PhD
Loma Linda University Health
Loma Linda, CA
The purpose of this study is to determine the efficacy of Droxidopa for the treatment of fatigue in patients with parkinsonism by the Visual Analog Fatigue Scale (VAFS). This is a randomized, placebo-controlled, double-blind clinical trial for three months where half the subjects will receive a placebo and the other half will receive Droxidopa. Following this will be a wash-out period of 7 days, and then all subjects will receive Droxidopa for three months during the open-label phase.
Parkinsonism is a group of symptoms seen in several diseases, including Parkinson’s Disease. In parkinsonism, a patient may become stiff, have smaller and slower movements, develop a tremor (shaking of the arms or legs), have decreased facial expression, and have a softer voice.
Fatigue is a common symptom that causes suffering and stress in diseases that affect the brain. Over 50% of patients with Parkinsonism report fatigue as one of their top three symptoms that make their life more difficult. Currently, there are no evidence-based guidelines for treating fatigue in Parkinson’s Disease, and no effective medications or therapeutic modalities exist for fatigue symptoms in patients with Parkinson’s Disease.
Droxidopa (also known by the trade name NORTHERA) is a safe and well-tolerated medication that has been approved in the USA for the treatment of orthostatic dizziness or lightheadedness in patients with a clinical diagnosis of Symptomatic Neurogenic Orthostatic Hypotension associated with primary autonomic failure (Parkinson’s Disease and Multiple System Atrophy), Dopamine Beta Hydroxylase Deficiency, or Non-Diabetic Autonomic Neuropathy.
Fatigue may be due to diminished levels of norepinephrine in Parkinson’s Disease. The locus coeruleus, one of the major sources of norepinephrine, is affected during the preclinical phase of Parkinson’s Disease during stage 2 of Braak pathology staging. Norepinephrine is the final metabolite of dopamine. Therefore by adding exogenous norepinephrine, it may be possible to control some of the motor and non-motor symptoms of parkinsonism. Norepinephrine is the final metabolite of droxidopa, and it is still unclear if it passes the blood-brain barrier. This pilot study is to measure the efficacy and safety of droxidopa in Parkinsonism patients with fatigue.
Title: Complex Eye Movements in Parkinson’s Disease and Related Movement Disorders
Principal investigator: Hector Rieiro, PhD
Dignity Health / St. Joseph’s Hospital and Medical Center
Diagnosing Parkinson’s disease (PD) depends on the clinical history of the patient and the patient’s response to specific treatments such as levodopa. Unfortunately, a definitive diagnosis of PD is still limited to post-mortem evaluation of brain tissues. Furthermore, diagnosis of idiopathic PD is even more challenging because symptoms of PD overlap with symptoms of other conditions such as essential tremor (ET) or Parkinsonian syndromes (PSs) such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), or vascular Parkinsonism (VaP). Based on the principle that PD and PSs affect brain areas involved in eye movement control, this trial will utilize a platform that records complex eye movements and use a proprietary algorithm to characterize PSs. Preliminary data demonstrate that by monitoring oculomotor alterations, the process can assign PD-specific oculomotor patterns, which have the potential to serve as a diagnostic tool for PD.
This study will evaluate the capabilities of the process and its ability to differentiate PD from other PSs with statistical significance. In addition, this proposal aims to optimize the detection and analysis algorithms and then evaluate the process against neurological diagnoses of PD patients in a clinical study.
In Phase I, complex eye movements, including Fixation, Optokinetic Nystagmus (OKN), Guided Saccades, Microsaccades, Smooth Pursuit, and Pupillometry will be measured in 90 subjects (30 PD, 30 non-PD with other movement disorders (PSP, ET, CBD, etc.), and 30 normal defined as not having any symptoms of any neurological condition.) The patients will be classified according to clinical evaluations and clinical follow-ups performed by Dr. Holly Shill, the Lonnie and Muhammad Ali Parkinson Center Director at the Barrow Neurological Institute (Phoenix, AZ). A 3-way analysis will be performed to troubleshoot and optimize the detection and classification algorithms. At this stage, these results will only be used for the evaluation of the diagnostic capability of the tool and not to treat or diagnose the patient. The product is portable with the potential to be an accurate tool to diagnose PD. This tool will provide substantial support to neurologists by validating or complementing the clinical tests currently used to diagnose PD. Successful diagnosis of PD can open new avenues for diagnosing other neurological conditions.