NBIA stands for Neurodegeneration with Brain Iron Accumulation. 

Formerly known as Hallervorden-Spatz disease or syndrome.

 

NBIA is a group of rare, genetic neurological disorders characterized by abnormal accumulation of iron in the basal ganglia. The basal ganglia is a collection of structures deep within the base of the brain that assist in regulating movements.

 

The exact relationship between iron accumulation and the symptoms of NBIA is not fully understood.

The hallmark clinical manifestations of NBIA relate to the body’s muscle function and feature a progressive movement disorder.

The frequency of NBIA in the general population is estimated between one to three people per 1 million individuals.

Because NBIA disorders are so rare, they  often go unrecognized, underdiagnosed or misdiagnosed.

 

NBIA is progressive and, at this time, there is no cure.

CHARACTERISTICS OF NBIA DISORDERS

Symptoms associated with all forms of NBIA

  • Dystonia refers to  involuntary muscle cramping that may force certain body parts into unusual, and sometimes painful, movements and positions.  Dystonia can affect the muscles in the mouth and throat, affecting speech and swallowing.  Dystonia can also affect the muscles of the eyelids, resulting in excessive blinking and involuntary closing of the eyelids. Moreover, dystonia can also affect the muscles of the neck resulting in abnormal movements and positions of the head and neck.

  • Choreoathetosis is a condition characterized by involuntary, rapid, jerky movements (chorea) occurring in association with relatively slow, sinuous, writhing motions (athetosis).

  • There may be stiffness in the arms and legs because of continuous resistance to muscle relaxing (spasticity) and abnormal tightening of the muscles (muscular rigidity). Spasticity and muscle rigidity usually begin in the legs and later develop in the arms.

  • Parkinsonism is a condition marked by tremor, slowness, rigidity and poor balance.

  • Most forms of NBIA involve eye disease. The most common problems are degeneration of the retina and optic atrophy.  In NBIA, early signs of retinal degeneration may be poor night vision or tunnel vision. It can eventually cause significant loss of vision. 

  • Optic atrophy affects the optic nerve.  Vision can become blurry, side vision or color vision may be abnormal, the pupil may not work properly, or there may be decreased lightness in one eye compared to the other. Eventually, optic atrophy can cause blindness.

  • cerebral atrophy and cerebellar atrophy, which refers to a general loss of brain cells and tissue are also frequently observed. 

  • Some forms of NBIA involve delays in development, mainly pertaining to motor skills (movement). Although cognitive decline occurs in some types of the disorder. 

 

Onset of NBIA

  • Ranges from infancy to adulthood.

  • Progression can be rapid or slow with long periods of stability.

  • Symptoms may vary greatly from case to case, partly because the genetic cause may differ between families. Also, different changes (mutations) within a gene could lead to a more or a less severe presentation.  The factors that influence disease severity and the rate of progression are still unknown.

  • Usually individuals with NBIA do develop increasing disabilities during the course of the disease.

 

Genetics

Of the eleven forms of NBIA currently identified, all but two are recessive.

 

Our genes exist in pairs (one coming from the mother and one coming from the father), we normally carry two working copies of each gene. When one copy of a recessive gene has a change (mutation) in it, the person should still have normal health. That person is called a carrier.

Recessive diseases only occur when both parents are carriers for the same condition and then pass their changed genes on to their child. Statistically, there is a one in four chance that two carriers would have an affected child. There is a two in four chance the parents would have a child who is also a carrier, and there’s a one in four chance they would have a child who did not receive the gene mutation.

Therapies

 

  • Since there is no treatment, or cure for NBIA disorders, treatment of NBIA is directed towards the specific symptoms that appear in each individual.

 

  • A team approach of specialists may be required.  Specialists can include: a family physician, pediatrician, neurologist, pulmonologist, ophthalmologist, orthopedist, gastroenterologist and clinical geneticist.  This team approach may also include supportive therapy, such as physical therapy, exercise physiology, occupational therapy and speech therapy. In addition, many families may benefit from genetic counseling.

  • Baclofen is the most common medication used for the relief of dystonia.  

  • The anti-cholinergic agent trihexyphenidyl (Artane) is a second medication that may be taken alone or in combination with baclofen. The combination of baclofen and artane has been found useful for many people with PKAN.

  • Levodopa/carbidopa (Sinemet) has been helpful for some patients with idiopathic NBIA, although it has not appeared to be helpful for PKAN patients.

  • Further muscle-relaxing medication include benzodiazepines such as diazepam (Valium) and lorazepam (Ativan).

  • Individuals experiencing seizures usually benefit from standard anti-convulsive drugs.

 

  • Standard approaches to pain management are generally recommended.

  • Over-the-counter fiber supplements and stool softeners can often improve the discomfort from constipation, which is common in NBIA disorders.

  • Injection of botulinum toxin (Botox) into muscles affected by dystonia can also provide relief for several months at a time because the botilinum causes temporary weakness of muscles that have involuntary contractions.

  • Deep Brain Stimulation (DBS) is another treatment used to control dystonia.  DBS is performed by implanting electrodes into the brain with a programmable device (neurostimulator) under the skin of the chest or abdomen. The neurostimulator sends pulses to targeted areas of the brain thus altering the pathological patterns of activity in the basal ganglia that cause the muscles to move in painful ways. DBS has been tried on several NBIA individuals with some good results, although it is unclear whether there is a long-term benefit.

The benefits and limitations of any of the above treatments should be discussed in detail with a physician.

Please visit the NBIA Disorders Association website, which was used as a primary source for the above information.

What is NBIA?