Neurodegeneration with brain iron accumulation
Abstract
PURPOSE OF REVIEW: Recent years have witnessed the discoveries of several genes causing neurodegeneration with brain iron accumulation (NBIA) and subsequently their novel classification scheme was suggested. The first results of treatments with modern chelating drugs are also being published. RECENT FINDINGS: Most recently, mutations in the c19orf12 gene encoding a mitochondrial protein of unknown function were identified in patients suffering from hitherto unknown NBIA presenting with a clinical phenotype similar to pantothenate kinase-associated neurodegeneration (PKAN) but with a slightly later onset. A case study has shown that mutations in the fatty-acid 2-hydroxylase gene may lead to various phenotypes combining the features of leukodystrophy and NBIA, supporting that abnormal metabolism of myelin and iron accumulation may have a common cause. A phase-II pilot study did not find any clinical improvement after chelating treatment in a group of PKAN patients. However, benefits of chelating treatment have been observed in individual patients with PKAN and idiopathic NBIA in another study. SUMMARY: This review gives an outline of the clinical presentations of recently discovered NBIA syndromes and summarizes the clues to their differential diagnosis. While chelating treatment still remains experimental, advances have been made regarding the indications of deep brain stimulation in symptomatic treatment of NBIAs manifesting with generalized dystonia.
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In other rare genetic diseases of the neurodegeneration with brain iron accumulation group, mutations disrupt proteins with cellular functions different from iron metabolism, and the mechanisms that result in brain iron overload are undefined.
“In other rare genetic diseases of this group, such as pantothenate kinase-associated neurodegeneration, phospholipase A2G6-associated neurodegeneration, and Kufor-Rakeb disease, mutations disrupt proteins with cellular functions different from iron metabolism, and the mechanisms that result in brain iron overload are undefined.169–173”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [171]
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The role of iron in brain ageing and neurodegenerative disorders
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- Authors
- Dusek, P., & Schneider, S. A.
- Affiliations
- University of Lübeck (DE)
- Venue
- Current Opinion in Neurology
- Published
- 2012-08
- Volume
- 25
- Issue
- 4
- Pages
- 499-506
- ISSN
- 1350-7540 (ISSN-L)
- OpenAlex
- W2003148596
- Cited by
- 39
- References
- 43
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 6 · 2018: 1 · 2016: 2 · 2015: 2 · 2014: 8 · 2013: 9
- FWCI
- 0.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- neurodegeneration with brain iron accumulation, pantothenate kinase-associated neurodegeneration, leukodystrophy, iron accumulation, chelation therapy, deep brain stimulation, dystonia, differential diagnosis, myelin metabolism
- MeSH terms
- Brain, Diagnosis, Differential, Humans, Iron, Iron Chelating Agents, Mutation, Neurodegenerative Diseases, Mitochondrial Proteins
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