Neurodegeneration with brain iron accumulation

Neurodegeneration with brain iron accumulation (NBIA), is a heterogeneous group of rare genetic disorders characterized by accumulation of iron in the basal ganglia, which results in variable neurological disorders including extrapyramidal symptoms, neuropsychiatric and visual symptoms.

Numerous genes (at least 10) have been identified, resulting in a variety of specific diseases ³:

• pantothenate kinase-associated neurodegeneration (PKAN)

  • most common form accounting for 35-50% of NBIA

  • previously known as Hallervorden-Spatz syndrome 

• PLA2G6-associated neurodegeneration (PLAN)

  • accounts for ~20% of NBIA

• mitochondrial membrane protein-associated neurodegeneration (MPAN)

  • accounts for ~6-10% of NIBA

• beta-propeller protein-associated neurodegeneration (BPAN)

  • accounts of 1-2% of NIBA

• infantile neuroaxonal dystrophy (INAD) / atypical neuroaxonal dystrophy (NAD)

• aceruloplasminaemia

• COASY protein-associated neurodegeneration (COPAN)

• fatty acid hydroxylase-associated neurodegeneration (FAHN)

• Kufor-Rakeb syndrome

• neuroferritinopathy

• Woodhouse-Sakati syndrome

Epidemiology

No single demographic is affected, and epidemiology varied depending on the specific condition, ranging from infancy to old age ³. 

Clinical presentation

Patients with NBIA suffer from a variety of neurological symptoms and signs including ³: 

• extrapyramidal symptoms

  • dystonia, muscular rigidity, spasms, parkinsonism

• neuropsychiatric symptoms

• optic atrophy

• retinal degeneration

Radiographic features

Radiographic features will vary among the various entities, but can broadly be thought of as ³:

• basal ganglia signal abnormalities

• cerebellar and cerebral atrophy

CT

Look for any calcifications in the brain. This is to differentiate calcification and iron deposition on MRI ⁴.

MRI

• T1: three-dimensional T1 images to look for brain morphology changes, and atrophy. T1-weighted images are useful to look for metallic deposits such as copper and iron molecular complexes that appear hyperintense ⁴

• T2/FLAIR: evaluate white matter changes, gliosis, and cavitations ⁴

• T2*/SWI: microscopic iron depositions especially hypointensities in the bilateral global pallidus ​⁴

Treatment and prognosis 

Although therapies will vary, dystonia is being treated with deep brain stimulation as well as oral or intrathecal baclofen ³. 

Renewed interest in iron chelation is now present with the development of deferiprone ³.