Neurodegeneration with brain iron accumulation
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Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurological disorders in which iron accumulates in the basal ganglia, resulting in progressive dystonia, Parkinsonism, spasticity, optic atrophy or retinal degeneration and neuropsychiatric abnormalities. NBIA have been associated with genes in synapse and lipid metabolism related pathways. Describes a group of disorders characterized by an accumulation of brain iron and the presence of axonal spheroids in the central nervous system. Iron accumulation can occur any where in the brain, with accumulation typically occurring in globus pallidus, substantia nigra, pars reticula, striatum and cerebellar dentate nuclei. Symptoms can include various movement disorders, seizures, visual disturbances, and cognitive decline, usually in combination. The known causes of NBIA disorders are mutation in genes directly involved in iron metabolism, impaired phospholipid and ceramide metabolism, lysosomal disorders, as well as mutations in genes with unknown functions. Onset can occur at different ages, from early childhood to late adulthood. Magnetic resonance imaging (MRI) is used to distinguish between the different forms of NBIA due to the accumulation of iron in different areas of the brain. Patients typically fall into two different categories: (1) early onset, rapid progression or (2) late onset, slow progression. The first type is considered to be the classic presentation, while they second type is the atypical presentation. Phenotypes of the different disorders appear to be dependent on age, i.e. amount of iron accumulation, cognitive ability.
An effective treatment has yet to be found. In many cases electrical stimulation of the globus pallidus has been shown to produce improvement of dystonia severity, however is has not been shown to improve neurodegeneration. There is often overlap in the phenotypes of the symptoms both between different NBIA disorders and between NBIA and other disorders, leading to misdiagnosis and sometimes treatment. Treatments typically treat or ameliorate the symptoms and do not address the accumulation of iron. Psychotherapy, such as dopaminergic drugs, anticholinergics, tetrabenazine, are often used to treat the symptoms but do not improve the long term outcome of the patient.
The group includes the following disorders:
- Pantothenate kinase-associated neurodegeneration (PKAN) also known as neurodegeneration with brain iron accumulation 1 (NBIA1) and Hallervorden–Spatz syndrome
- PLAN (PLA2G6-associated neurodegeneration)
- MPAN (Mitochondrial membrane protein-associated neurodegeneration)
- BPAN (Beta-propeller protein-associated neurodegeneration)
- FAHN (Fatty acid hydroxylase-associated neurodegeneration)
- Kufor–Rakeb syndrome
- Woodhouse–Sakati syndrome
- CoPAN (CoA synthase protein-associated neurodegeneration)
- Idiopathic NBIA
- Neurodegeneration with brain iron accumulation 2B (NBIA2B)
- Neurodegeneration with brain iron accumulation 3 (NBIA3)
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