From the Guidelines
Neurodegeneration with Brain Iron Accumulation (NBIA) is a distinct group of conditions characterized by excess iron deposition in the basal ganglia with progressive neuronal degeneration, as noted in the 2020 study by the Journal of the American College of Radiology 1. NBIA is a group of rare genetic disorders that lead to excessive iron buildup in the brain, particularly in the basal ganglia. The most common subtype is NBIA type 1, also known as pantothenate kinase-associated neurodegeneration, which classically presents in the first decade with slowly progressive gait disturbances, dystonia, dysarthria, spasticity, and pyramidal tract signs 1. Some key characteristics of NBIA include:
- Excessive iron deposition in the basal ganglia
- Progressive neuronal degeneration
- Rare genetic disorders
- Four defined subtypes, with NBIA type 1 being the most common
- Classic presentation in the first decade with gait disturbances, dystonia, and other neurological symptoms Management of NBIA typically involves supportive care, including medications to control movement disorders, physical therapy, occupational therapy, speech therapy, and nutritional support. The primary goal of treatment is to manage symptoms and slow disease progression, as there is currently no cure for NBIA, and iron chelation therapy with deferiprone has shown some benefit in certain subtypes 1. Imaging modalities such as MRI are preferred over CT for suspected NBIA due to their higher sensitivity to basal ganglia iron accumulation, although CT may be helpful in distinguishing between calcium and iron deposition in the brain 1. Genetic counseling is recommended for affected families, and the progressive nature of NBIA stems from the neurotoxic effects of iron accumulation, which causes oxidative stress and neuronal damage, leading to the characteristic movement disorders, cognitive decline, and other neurological symptoms associated with these conditions.
From the Research
Definition and Characteristics of NBIA
- Neurodegeneration with Brain Iron Accumulation (NBIA) is a heterogeneous group of progressive neurodegenerative diseases characterized by iron deposition in the globus pallidus and the substantia nigra 2.
- NBIA disorders present with a wide spectrum of clinical symptoms such as movement disorder signs (dystonia, parkinsonism, chorea), pyramidal involvement (e.g., spasticity), speech disorders, cognitive decline, psychomotor retardation, and ocular abnormalities 2, 3, 4.
Types of NBIA
- The four most common forms of NBIA are pantothenate kinase-associated neurodegeneration (PKAN), phospholipase A2 group VI (PLA2G6)-associated neurodegeneration (PLAN), beta-propeller protein-associated neurodegeneration (BPAN), and mitochondrial membrane protein-associated neurodegeneration (MPAN) 2, 3, 4.
- Other forms of NBIA include neuroferritinopathy, aceruloplasminemia, Kufor-Rakeb syndrome, fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN), and Woodhouse-Sakati syndrome 4.
Diagnosis and Treatment
- Brain iron accumulation can be diagnosed through MRI imaging and is hypothesized to be the cause of oxidative stress, leading to the degeneration of brain tissue 3, 4.
- There are no causative therapies for NBIA, but iron chelators have been shown to have potential toward treating NBIA 2, 3, 5.
- Treatment remains largely symptomatic, but new drugs are in the pipeline, including iron chelators such as deferiprone, desferasirox, and deferoxamine 2, 3.