Neuroferritinopatía (Neuroferritinopathy) - Gen FTL

The neuroferritinopatía is a disease that causes progressive accumulation of iron in the brain. Basal ganglia, involved in the regulation of the movement are particularly affected. For this reason, patients with neuroferritinopatía begin to have problems in moving about 40 years, although this may be extended to age 60. It is likely to require several years until they begin to manifest symptoms, which could open a path in therapeutic interventions. Problems include involuntary, jerky movements, tremors, rhythmic movements, ataxia, dystonia, etc. They may also have difficulties in speech (dysarthria) and swallowing (dysphagia). In most cases intelligence is not affected , but as the disease progresses, some people develop dementia and personality changes such as reducing inhibitions and difficulty controlling emotions.

Its population incidence is unknown, since it is a pathology of recent discovery, but it is known that is underdiagnosed and misdiagnosed in many cases as Huntington 's , Parkinson 's or similar disease. The use of additional diagnostic methods based on sequencing would help significantly to improve reliability of diagnosis.

This process is due to mutations in the FTL gene, located on the long arm of chromosome 19 (19q13.33). This gene is involved in encoding ferritin light chains, which constitute a subunit ferritin protein. This region is called IRE ( "Iron Responsive Element" -elemento that responds to iron) and has the function of binding to cytoplasmic proteins IRP ( "Iron Regulatory Proteins" regulatory - proteins of iron). In case of iron deficiency, IRP proteins acquire a high affinity for the IRE and act by inhibiting the synthesis of ferritin light chains. IRE-IRP interaction occurs on a ring structure consisting of five pairs in one end of the IRE. Thus, mutations that alter the morphology of this structure reduced or canceled the ability to regulate the synthesis of ferritin light chains, to stop operating the negative feedback system responsible for regulation. Therefore ferritin it is synthesized in excess and results in the formation of complexes that accumulate, leading to increased concentrations of serum ferritin, liver, lymphoid cells and lens, causing early onset cataracts.

They have identified at least 4 mutations in the FTL gene in people with neuroferritinopatía. These mutations affect gene exon 4. The most common mutation detected in affected individuals inserts the adenine nucleotide between the 460 and 461 positions in the gene sequence. It is believed that most families with this mutation are descended from a common ancestor that lived in northwest England before 1800. The other three known mutations are each in a single person or family affected by neuroferritinopatía. It is believed that mutations in the gene responsible for neuroferritinopatía FTL reduce the ability to store ferritin iron, which results in excess release of iron in neurons. The cells may respond by producing more ferritin in an attempt to manipulate the free iron. Excess iron and ferritin accumulate in the brain, especially in the basal ganglia, resulting in movement problems and other neurological changes observed in affected individuals.

This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for the disease to be expressed. In most cases, an affected person has a parent with the disease. Other cases may be due to new mutations in the gene and occur in people with no history of disease in your family.

Tests in IVAMI: in IVAMI perform detection of mutations associated with neuroferritinopatía, by complete PCR amplification of exons FTL gene, and subsequent sequencing. We recommend starting the study by exon 4 of the gene where mutations identified so far are located, thereby reducing the cost and time of execution. If not detected any mutation in this region would proceed to study the remaining exons.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).