is of unknown origin, although it is suspected to be genetic.
For many families, the person diagnosed with NBIA is the first and only affected individual, so it is difficult to know whether there is a specific pattern of inheritance. It is thought that most of these cases are probably recessive because some families have more than one affected child and idiopathic NBIA is more common in families in which the parents are related, such as distant cousins. That would make it more likely that they share a recessive gene.
The symptoms are more varied because there are probably several different causes of neurodegeneration for individuals in this group. As with other forms of NBIA, the idiopathic form features early- and late-onset types. About 35 percent of those diagnosed with NBIA are believed to be in this group.
Individuals affected with idiopathic NBIA disorder fall into one of the two categories
- Had not genetic testing at early stages of NBIA diagnosis which can take a long time to complete and often begins with the discovery of iron accumulation in the brain on an MRI. High brain iron levels alone are not enough to give a diagnosis of NBIA, but they can make a doctor suspect that NBIA is a possible diagnosis. The next step will likely be a series of clinical tests to check for other NBIA symptoms and genetic testing. The genetic testing is done by collecting a blood sample and checking to see if any of the genes have a change that is known to cause NBIA. Particular gene changes are associated with certain NBIA disorder, so figuring out which gene is altered will let doctors know which NBIA disorder you have.
- Had genetic testing probably many or all the known gene changes that can cause NBIA have been tested. The genetic testing not revealing any known NBIA disorder subtypes are classified as “idiopathic” NBIA. Idiopathic means the cause is unknown. Although an MRI may show evidence of increased brain iron, and symptoms may point to NBIA, an underlying gene change is sometimes not found. The testing procedure isn’t advanced enough to detect the genetic change or the NBIA was caused by a change in a gene it has not discovered yet.
Diagnosis
Suspicion of NBIA usually arises when an MRI of the brain shows excessive iron accumulation, along with a movement disorder. Depending on symptoms, genetic testing is done to rule out other forms of NBIA. If all are negative and the findings are characteristic of NBIA, then the diagnosis of Idiopathic NBIA is given until further evidence of the genetic origin or another cause is determined.
Evaluations to determine the extent of the disease
Neurologic examination for movement disorders,
- Dystonia, rigidity, spasticy
- Choreoathetosis, involuntary movements that include contractions, twisting and writhing.
- Walking ability
- Speech
Eye exam
- Retinopathy (damage to the small blood vessels in the retina)
- Optic atrophy (the loss of some or most of the fibers of the optic nerve).
- Developmental delay, motor and cognitive
Surveillance
- Assessment to see if physical therapy, occupational therapy and/or speech therapy are warranted.
- Assessment of behavior and neuropsychiatric changes.
- Medical genetics consultation.
TREATMENT
Affected individuals may need a feeding tube or other assistance to achieve adequate nutrition. Other therapies and medication can be recommended by a team of medical experts.
Cause
Testing to find the gene responsible for an individual form of NBIA may be pursued.
Research
Researchers continue their search for remaining genes that cause NBIA disorders and much progress is being made with new technology. Affected individuals diagnosed with Idiopathic NBIA might want to participate in the International Patient Registry. If a new gene is found by researchers, the person’s samples will be examined to see if they have mutations and their form of NBIA identified. A newer technology called whole exome sequencing can help shed light on these cases. This type of testing may be available as research or as a clinical test.
There are two research repository, NBIAcure in USA and the international NBIA patient registry in Europe for other gene changes responsible for NBIA that have not yet been discovered.
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Prenatal Testing
In the absence of a known genetic mutation, testing during pregnancy to assess risk is not possible.