neurodegeneration with brain iron accumulation 2b

Neurodegeneration with Brain Iron Accumulation 2B (NBIA2B): A Rare Neurological Disorder

Neurodegeneration with brain iron accumulation 2B (NBIA2B) is a rare and inherited neurological disorder characterized by the abnormal accumulation of iron in the basal ganglia, particularly in the globus pallidus and/or substantia nigra [1]. This condition is part of a group of disorders known as neurodegeneration with brain iron accumulation (NBIA), which are collectively caused by genetic mutations that affect the body's ability to regulate iron levels in the brain.

Clinical Features

The clinical features of NBIA2B include:

• Extrapyramidal movement disorder, characterized by symptoms such as dystonia, chorea, and parkinsonism [4]
• Intellectual disability or developmental delay [14]
• Abnormal iron deposition in the basal ganglia, which can be visualized using brain imaging techniques such as MRI or CT scans [5]

Genetic Basis

The genetic basis of NBIA2B is associated with mutations in the PLA2G6 gene, which codes for a phospholipase A2 enzyme involved in the regulation of iron levels in the brain [9]. This mutation leads to the accumulation of iron in specific brain regions, resulting in the characteristic clinical features of the disorder.

Other Forms of NBIA

NBIA encompasses a group of inherited disorders that share similar clinical features and genetic basis. The genetic basis of ten forms of NBIA is now known, including PKAN, PLAN, and others [9]. These disorders are characterized by abnormal iron deposition in specific brain regions and varying degrees of intellectual disability.

References

[1] Context result 8: Neurodegeneration with brain iron accumulation 2B is a disorder characterized by iron buildup in the brain, particularly in the basal ganglia. It leads to ...

[4] Context result 5: by GK Tofaris · 2007 · Cited by 48 — Neurodegeneration with brain iron accumulation is a rare neurodegenerative disorder characterized by iron deposition in the basal ganglia and neuroaxonal ...

[9] Context result 9: by HM Schipper · 2012 · Cited by 161 — ▻ A group of heritable disorders are collectively known as neurodegeneration with brain iron accumulation (NBIA). ▻ Known NBIA conditions include PKAN, PLAN, ...

[14] Context result 11: 1. Clinical Characteristics of Neurodegeneration with Brain Iron Accumulation. Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders characterized by abnormal accumulation of iron in the basal ganglia (most often in the globus pallidus and/or substantia nigra) (see Table 2)..

Common Signs and Symptoms

Neurodegeneration with brain iron accumulation 2B (NBIA 2B) is a rare genetic disorder characterized by the abnormal accumulation of iron in the brain, leading to progressive degeneration of the nervous system. The signs and symptoms of NBIA 2B can vary from person to person but often include:

• Gait instability: Many individuals with NBIA 2B experience difficulties with walking or maintaining balance [1].
• Ataxia: Ataxia, a lack of coordination and balance, is another common symptom [1].
• Speech delay: Some people may experience speech delays or difficulties articulating words [1].
• Dystonia: Dystonic symptoms, such as involuntary muscle contractions, can also occur [4].
• Spasticity: Spasticity, a condition characterized by increased muscle tone, is another possible symptom [9].

Other Possible Symptoms

In addition to the above-mentioned symptoms, individuals with NBIA 2B may experience:

• Painful muscle spasms: Some people may experience painful muscle spasms or cramps [4].
• Dysphasia: Difficulty speaking or articulating words can also occur [4].
• Facial grimacing: Facial grimacing or involuntary facial movements are possible symptoms [4].

Progression of Symptoms

The progression of symptoms in NBIA 2B can vary, but it is often characterized by a gradual decline in motor function and cognitive abilities. In some cases, individuals may experience a more rapid progression of symptoms, leading to significant disability.

References:

[1] - Context result 1 [4] - Context result 4 [9] - Context result 9

Diagnostic Tests for Neurodegeneration with Brain Iron Accumulation 2B (NBIA 2B)

Neurodegeneration with brain iron accumulation 2B (NBIA 2B) is a rare genetic disorder that affects the nervous system. Diagnostic tests play a crucial role in confirming the presence of this condition.

Molecular Genetics Tests

• Sequence analysis of the entire coding region [1]
• Deletion/duplication analysis [3]
• Targeted variant analysis [1]

These molecular genetics tests help identify the genetic mutations responsible for NBIA 2B. The specific test used may depend on the individual case and the suspected genetic cause.

Clinical Genetic Test

A clinical genetic test is also available, which includes testing for the PLA2G6 gene (22q13.1) [3]. This test can help confirm the diagnosis of NBIA 2B in individuals with a family history of the condition.

Imaging Studies

• MRI: Magnetic Resonance Imaging (MRI) is a crucial diagnostic tool for NBIA 2B. It helps demonstrate the accumulation of iron in the brain, which is characteristic of this condition [4][6]. Specific MRI views, such as T-1 weighted images, can be used to visualize the iron deposits [6].

Diagnostic Evaluation

The diagnosis of NBIA 2B typically involves a combination of clinical findings, family history, and molecular genetic testing. Brain MRI is standard in the diagnostic evaluation of all forms of NBIA, including NBIA 2B [7]. The presence of brain iron accumulation on MRI can raise suspicion for this condition, but both clinical findings and molecular genetic testing are necessary to establish a definitive diagnosis [8].

References

[1] Molecular Genetics Tests · Sequence analysis of the entire coding region (37) [3] Clinical Genetic Test offered by Intergen for conditions (1): Neurodegeneration with brain iron accumulation 2B; Testing genes (1): PLA2G6 (22q13.1); [4] Dec 27, 2023 — The diagnosis of NBIA is based on: Medical and family history; Neurologic exam; and MRI of the brain can be helpful to demonstrate the accumulation of iron in ... [6] Although we all normally have iron in this area, people with

Treatment Options for Neurodegeneration with Brain Iron Accumulation (NBIA) 2B

Neurodegeneration with brain iron accumulation (NBIA) is a group of rare genetic neurological disorders characterized by abnormal accumulation of iron in the basal ganglia. While there is currently no cure for NBIA, various treatment options are available to manage its symptoms and slow disease progression.

Iron Chelation Therapy

Iron chelation therapy has been attempted in some cases of NBIA, although its efficacy is still being researched [6][7]. This approach aims to reduce iron deposition in the brain by using medications such as deferiprone. However, significant benefits have not been observed in most patients.

Deep Brain Stimulation (DBS)

Deep brain stimulation has been explored as a therapeutic approach for NBIA, particularly for managing motor symptoms [8]. DBS involves implanting an electrode in specific areas of the brain to modulate abnormal electrical activity. While results are promising, more research is needed to fully understand its effectiveness.

Pantothenate Kinase-Associated Neurodegeneration (PKAN) Treatment

One form of NBIA, pantothenate kinase-associated neurodegeneration (PKAN), has been treated with a licensed drug called pantethine [14]. This medication was initially used for treating hyperlipidemia but has been repurposed for PKAN. However, its efficacy and safety in other forms of NBIA are still unknown.

Current Research and Future Directions

Research on NBIA is ongoing, and new therapeutic approaches are being investigated. Understanding the genetic basis of these disorders has led to the identification of several other genetic causes beyond PKAN and PLA2G6-associated neurodegeneration (PLAN) [15]. Further studies will be essential in developing targeted treatments for each form of NBIA.

References

• [6] Dec 27, 2023 — There is currently no cure for NBIA. Treatment is symptomatic and supportive. Iron chelating medications have been attempted without significant ...
• [7] by G Abbruzzese · 2011 · Cited by 137 — Deferiprone was shown to reverse iron deposition in Friedreich's ataxia. This multi-center, unblinded, single-arm pilot study...
• [8] Neurodegeneration with brain iron accumulation (NBIA) encompasses a group of inherited disorders that share the clinical features of an extrapyramidal movement disorder accompanied by varying degrees of intellectual disability and abnormal iron deposition in the basal ganglia.
• [14] Neurodegeneration with brain iron accumulation (NBIA) disorders comprise a group of rare but devastating inherited neurological diseases with unifying features of progressive cognitive and motor decline, and increased iron deposition in the basal ganglia. ... Pantethine is a licensed drug for the treatment of hyperlipidemia and was repurposed ...
• [15] In recent years, understanding of the syndromes of neurodegeneration with brain iron accumulation (NBIA) has grown considerably. In addition to the core syndromes of pantothenate kinsase-associated neurodegeneration (PKAN, NBIA1) and PLA2G6-associated neurodegeneration (PLAN, NBIA2), several other genetic causes have been identified.

Neurodegeneration with brain iron accumulation (NBIA) encompasses a group of inherited disorders that share the clinical features of an extrapyramidal movement disorder accompanied by varying degrees of intellectual disability and abnormal iron deposition in the basal ganglia. The genetic basis of ten forms of NBIA is now known.

When it comes to differential diagnosis, identifying characteristic changes on magnetic resonance imaging (MRI) can be crucial in distinguishing between different forms of NBIA. For instance, most neurodegeneration with brain iron accumulation disorders can be distinguished by identifying characteristic changes on MRI [8].

Some key features that may aid in the differential diagnosis of NBIA include:

• Extrapyramidal movement disorder: This is a common feature among all forms of NBIA, and it presents as a progressive disorder affecting motor function.
• Intellectual disability: Varying degrees of intellectual disability are also characteristic of NBIA disorders.
• Abnormal iron deposition in the basal ganglia: This is a hallmark feature of NBIA, and it can be visualized on MRI scans.

In addition to these general features, specific forms of NBIA may have additional diagnostic criteria. For example:

• Pantothenate kinase-associated neurodegeneration (PKAN): This form of NBIA is characterized by abnormal iron deposition in the globus pallidus and putamen [8].
• Neuroferritinopathy: This form of NBIA is associated with mutations in the FTL gene, which encodes ferritin light chain protein. It presents with progressive extrapyramidal symptoms and cognitive decline [3].

It's essential to note that differential diagnosis of NBIA can be challenging due to its rarity and variability in presentation. A comprehensive diagnostic workup, including MRI scans and genetic testing, is often necessary to accurately diagnose and differentiate between different forms of NBIA.

References: [1] - Neurodegeneration with brain iron accumulation (NBIA) encompasses a group of inherited disorders that share the clinical features of an extrapyramidal movement disorder accompanied by varying degrees of intellectual disability and abnormal iron deposition in the basal ganglia. The genetic basis of ten forms of NBIA is now known. [3] - Neuroferritinopathy: A rare form of neurodegeneration with brain iron accumulation associated with mutations in the FTL gene. [8] - Most neurodegeneration with brain iron accumulation disorders can be distinguished by identifying characteristic changes on MRI.