Neurodegeneration with brain iron accumulation

Source: Wikipedia, the free encyclopedia.
Neurodegeneration with brain iron accumulation
Other namesNBIA
SpecialtyNeurology Edit this on Wikidata

Neurodegeneration with brain iron accumulation is a heterogenous group of inherited

neuropsychiatric, or diverse neurologic abnormalities.[1]
Some of the NBIA disorders have also been associated with several genes in synapse and lipid metabolism related pathways.
axonal spheroids in the central nervous system.[3]

Iron accumulation can occur anywhere in the brain, with accumulation typically occurring in globus pallidus, substantia nigra, pars reticula, striatum and cerebellar dentate nuclei.[4] Symptoms can include various movement disorders, neuropsychiatric issues, seizures, visual disturbances, and cognitive decline, usually in different combinations.[4] Ten to fifteen genetic NBIA disorders involving various cell processes have been identified: iron metabolism, coenzyme A biosynthesis, phospholipid metabolism, ceramide metabolism, lysosomal disorders, as well as mutations in genes with unknown functions.[5][4] Onset can occur at different ages, from early childhood to late adulthood.[4]

As of 2021 there were no curative treatments for any of the NBIA disorders, though several medications have been subject to clinical trial including the iron chelator deferiprone.[5]

Variants

Overview of monogenic NBIA disorders[5][6][7]
NBIA variant Gene Inheritance
Pantothenate kinase-associated neurodegeneration (PKAN)[8] PANK2 autosomal recessive
PLA2G6-associated neurodegeneration (PLAN)[9] PLA2G6 autosomal recessive
Mitochondrial membrane protein-associated neurodegeneration (MPAN)[10] C19orf12 autosomal recessive or dominant
Beta-propeller protein-associated neurodegeneration (BPAN)[11]
 WDR45 X-linked dominant (mostly de novo mutations)
Fatty acid hydroxylase-associated neurodegeneration (FAHN)[12] FA2H autosomal recessive
Kufor–Rakeb syndrome ATP13A2 autosomal recessive
Neuroferritinopathy FTL autosomal dominant
Aceruloplasminemia CP autosomal recessive
Woodhouse–Sakati syndrome DCAF17 autosomal recessive
COASY protein-associated neurodegeneration (CoPAN) COASY autosomal recessive
NBIA7[13] REPS1 autosomal recessive
NBIA8[13] CRAT autosomal recessive

Diagnosis

PET scans, and, in some cases, magnetic resonance imaging (MRI) (type of scans depending on the symptoms)[14] are used to distinguish between the different forms of NBIA due to the accumulation of iron in different areas of the brain.[15] Patients typically fall into two different categories: (1) early onset, rapid progression or (2) late onset, slow progression.[15] The first type is considered to be the classic presentation, while the second type is thought to be a more atypical presentation. Phenotypes of the different disorders appear to be dependent on age, i.e. amount of iron accumulation and cognitive abilities.[16]

Treatments

Effective disease-modifying treatments have not yet been found for any of the NBIA disorders.[5] Treatment is supportive and focused on improving symptoms: Dystonia is a common debilitating symptom and can be managed with oral medications, and sometimes with deep-brain electrical stimulation, therapy support for walking, eating, and manual tasks is essential. Later, in many of the diseases, slowing and stopping of movement (known as parkinsonism) can become common. Removal of iron, using medications known as iron chelators, has been tested in clinical trial but was not definitively shown to be effective.[17]

References

  1. PMID 30855105. {{cite book}}: |journal= ignored (help
    )
  2. PMID 26707700
    .
  3. PMID 18981035
    .
  4. ^
    PMID 22691760
    .
  5. ^
    PMID 34909266
    .
  6. PMID 23447832
    .
  7. PMID 25614780
    .
  8. PMID 20301663
    .
  9. PMID 20301718
    .
  10. PMID 24575447
    .
  11. PMID 28211668
    .
  12. PMID 21735565
    .
  13. ^
    PMID 29395073
    .
  14. ^ Brüggemann N. et al.: Recessively inherited parkinsonism: effect of ATP13A2 mutations on the clinical and neuroimaging phenotype. Arch Neurol. 2010 Nov;67(11):1357-63. doi: 10.1001/archneurol.2010.281.
  15. ^
    PMID 16775270
    .
  16. PMID 22704258
    .
  17. S2CID 186245765
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Neurodegeneration_with_brain_iron_accumulation&oldid=1208198534"