Neurodegeneration with brain iron accumulation.

Area of Science:

• Neurogenetics
• Rare diseases
• Neurodegenerative disorders

Background:

• Neurodegeneration with brain iron accumulation (NBIA) is a group of rare, inherited neurodegenerative disorders.
• NBIA disorders are characterized by iron accumulation in the basal ganglia, often detected via MRI.
• These conditions affect both children and adults, presenting with diverse clinical symptoms.

Purpose of the Study:

• To review the genetic basis of NBIA disorders.
• To highlight the diagnostic approaches and available genetic testing.
• To discuss the spectrum of NBIA conditions, from common to ultrarare.

Main Methods:

• Genetic analysis of patients with NBIA.
• Review of clinical and neuroimaging findings.
• Delineation of genotype-phenotype correlations.

Main Results:

• The genetic basis for most NBIA disorders is identified.
• Four common NBIA disorders are linked to mutations in PANK2, PLA2G6, C19orf12, and WDR45.
• Ultrarare forms are associated with mutations in CoASY, ATP13A2, and FA2H, collectively explaining ~85% of cases.
• Whole-exome sequencing is identifying new NBIA genes and aiding early diagnosis.

Conclusions:

• Genetic testing is available for the majority of NBIA disorders.
• Advances in genetic sequencing are expanding the understanding of NBIA.
• Early diagnosis and genetic identification are key for managing NBIA patients.