NBIA

Neurodegeneration with brain iron accumulation (NBIA) is a term that encompasses a group of disorders characterized by extrapyramidal symptoms and abnormal iron deposition in the deep basal ganglia. There are over 10 genes associated with NBIA, among which Pantothenate kinase-associated neurodegeneration (PKAN) represents the most common form of the disorder.

Pantothenate kinase-associated neurodegeneration (PKAN)

PKAN is an autosomal recessive disorder driven by mutation in PANK2 gene expressed in mitochondria. The neurodegeneration in this disease is thought to involve impaired phospholipid and fatty acid metabolism and mitochondrial dysfunction due to decreased PANK2 activity. In addition, since cysteine, a substrate of PANK2, is an iron chelator, its accumulation may cause iron deposition, further exacerbating the oxidative damage.

Clinical findings

Pigmentary retinopathy is a distinct finding exclusive to PKAN and does not occur in other forms of NBIA, whereas optic nerve atrophy suggests an alternate form of NBIA.

The classic form of PKAN typically manifests in childhood, frequently before the age of 6, initially presenting with dystonia along with pyramidal/extrapyramidal symptoms and cognitive impairment, and progresses in a stair-step fashion.

In contrast, the atypical form has a later onset, with an average age of 14 years, and features a slower progression compared to the Classic form. In the Atypical form, dystonia is mild and characterized by dysarthria, tautomania, psychiatric symptoms, and stooped posture.

Blood tests may occasionally reveal acanthocytosis, indicative of Neuroacanthocytosis.

References

1. Kruer, Michael C., et al. "Neuroimaging features of neurodegeneration with brain iron accumulation." American Journal of Neuroradiology 33.3 (2012): 407-414.