Patients who are diagnosed with neuroferritinopathy have abnormal iron accumulation in the brain within the neurons and glia of the striatum and cerebellar cortices. Along with the accumulation of iron in the brain, neuroferritinopathy typically causes severe neuronal loss as well. Secondary symptoms may also arise. It is possible that the initial iron accumulation will cause additional neuronal damage and neuronal death. The damaged neurons may be replaced by other cells in an effort to reverse the neurodegeneration. These cells often have a higher iron content. The breakdown of the blood brain barrier may also occur due to the loss of neurons and will subsequently allow more iron to access the brain and accumulate over time.Neuroferritinopathy is mainly seen in those who have reached late adulthood and is generally seen to slowly progress throughout many decades in a lifetime with the mean age of onset being 39 years old. A loss of cognition is generally only seen with late stages of the disease. Diagnosed patients are seen to retain most of their cognitive functioning until the most progressive stages of the illness sets in. Physical symptoms
Symptoms categorized as physically visible symptoms include chorea, dystonia, spasticity, and rigidity, all physical symptoms of the body associated with movement disorders. The symptoms accompanying neuroferritinopathy affecting movement are also progressive, becoming more generalized with time. Usually during the first ten years of onset of the disease only one or two limbs are directly affected.
Other genetic associations
A fourth gene associated with this condition is the proline-rich transmembrane protein 2 (PRRT2 gene) - an axonal protein associated with the exocytosis complex.A fifth gene associated with this condition is SLC4A4, which encodes the electrogenic NaHCO3 cotransporter NBCe1. Diagnosis
Diagnosis of FHM is made according to these criteria:
Two attacks of each of:Aura with motor weakness accompanied by either reversible visual symptoms (flickering lights, spots, lines, etc. ), reversible sensory symptoms (pins and needles, numbness, etc.) or speech symptoms
At least two occurrences of:One or more aura symptoms that develop over at least 5 minutes
These symptoms lasting more than 5 minutes and less than 24 hours
Headache beginning within 60 minutes of aura onset: These headaches can last 4–72 hours, occur on only one side of the head, pulsate, be of moderate to severe intensity, and may be aggravated by common physical activities such as walking. These headaches must also be accompanied by nausea/vomiting, phonophobia (avoidance of sound due to hypersensitivity), and/or photophobia (avoidance of light due to hypersensitivity).At least one close (first- or second-degree) relative with FHM
No other likely causeSporadic forms follow the same diagnostic criteria, with the exception of family history. In all cases, family and patient histories are used for diagnosis. Brain-imaging techniques, such as MRI, CAT scan, and SPECT, are used to look for signs of other familial conditions such as CADASIL or mitochondrial disease, and for evidence of cerebellar degeneration. With the discovery of causative genes, genetic sequencing can also be used to verify diagnosis (though not all genetic loci are known).