Neuroferritinopathy  is a genetic neurodegenerative disorder characterized by the accumulation of iron in the basal ganglia, cerebellum, and motor cortex of the human brain. Symptoms, which are extrapyramidal in nature, progress slowly and generally do not become apparent until adulthood. These symptoms include chorea, dystonia, and cognitive deficits which worsen with age.This disorder is autosomal dominant and is caused by mutations in the gene encoding the light chain subunit of the ferritin protein. Wild type ferritin functions as a buffer for iron, sequestering it and controlling its release. Thus, mutations in the light chain of ferritin result in the accumulation of iron in the brain which can be imaged using MRI. Currently, neuroferritinopathy is the only neurodegenerative disease with an iron accumulation in the brain classified as an autosomal dominant syndrome.Treatment of neuroferritinopathy is focused on managing symptoms associated with chorea and dystonia using standard medications for each. The disorder is progressive and symptoms become worse with age. Fewer than 100 cases of neuroferritinopathy have been reported since its identification in 2001. Its incidence has been largely localized to Northeast England suggesting a founder effect. Due to its genetic nature, current research is focused on therapeutic management of the symptoms caused by the disorder. Signs and symptoms
Neuroferritinopathy has several distinguishing signs and symptoms. These fall into two categories: diagnostic findings and physically visible symptoms. Diagnostic findings
Symptoms categorized as medically tested and diagnosed include iron accumulation in the brain, basal ganglia cavitation, and neurodegeneration.
Distinctive symptoms of neuroferritinopathy are chorea, found in 50% of diagnosed patients, dystonia, found in 43% of patients, and parkinsonism, found in 7.5% of patients. Full control of upper limbs on the body generally remains until late onset of the disease. Over time, symptoms seen in a patient can change from one side of the body to the opposite side of the body, jumping from left to right or vice versa. Another route that the physically visible symptoms have been observed to take is the appearance, disappearance, and then reappearance once more of specific symptoms.While these symptoms are the classic indicators of neuroferritinopathy, symptoms will vary from patient to patient. Causes
Neuroferritinopathy results from abnormal brain iron accumulation. This iron accumulation is due to mutations in the FTL polypeptide, which is responsible for encoding proteins involved in iron metabolism. Neuroferritinopathy is most commonly caused by a single insertion of the nucleotide adenine into the gene for L-chain ferritin which in turn, alters the carboxyl end of the entire protein chain. However, exact location of the insertion in the exon varies by family. Neuroferritinopathy may also be caused by the insertion of two extra nucleotide bases. The insertion of bases into the L-chain ferritin gene causes the chain to lengthen and alter the sequence of the amino acids found in the gene, also known as a frameshift mutation.These mutations result in decreased iron-binding ability. The oxidative damage caused by increased iron leads to apoptosis, or programmed cell death.