Acute necrotizing encephalopathy type 1 (Acute necrotizing encephalopathy type 1) - Gen RANBP2

Acute necrotizing encephalopathy type 1 is a rare type of encephalopathy develops after a viral infection. This process usually occurs in infancy or early childhood, although some people do not develop the disease until adolescence or adulthood. People with this condition usually show typical signs of infection such as fever, cough, congestion, vomiting and diarrhea for a few days. Following these flu - like symptoms, affected individuals develop neurological problems, including seizures, hallucinations, ataxia, or abnormal muscle tone. Finally, most affected individuals go into a coma, usually for a few weeks. The process is described as "acute" because the episodes of the disease are of limited duration.

People with acute necrotizing encephalopathy type 1 develop lesions in certain brain regions. As the disease progresses, these brain regions develop edema, hemorrhage, and later necrosis. The progressive brain damage and loss of tissue derived encephalopathy. Approximately one - third of individuals with acute necrotizing encephalopathy type 1 do not survive the illness and subsequent neurological decline. Of those who survive, approximately half has a permanent brain damage due to tissue necrosis, resulting in gait disturbance, speech and other basic functions. Eventually, many of these skills are recovered, but the loss of brain tissue is permanent. Others who survive their disease appear to recover fully. It is estimated that half of individuals with acute necrotizing encephalopathy type 1 are susceptible to recurrent episodes and have another infection that results in decreased neurological function; some people can have numerous episodes throughout their lives. Neurological function gets worse after each episode as more brain tissue is damaged.

Studies indicate that mutations in the gene RANBP2 (RAN binding protein 2) increase the risk of developing acute necrotizing encephalopathy RANBP2 type 1 gene, located on the long arm of chromosome 2 (2q12.3), encoding a protein normally it is associated with a protein complex known as the nuclear pore. The nuclear pore is located inside of the envelope, forming a channel that allows the transport of molecules inside and outside the core. The RanBP2 protein is attached to the nuclear pore in the outer core, which helps to regulate the transport of proteins and other molecules through the nuclear pore and also helps to modify proteins entering or exiting the core. When the protein is RanBP2 elsewhere in the cell, it plays multiple roles during cell division, including decomposition and formation of the nuclear envelope and dividing chromosomes. It is believed that RanBP2 protein binds to microtubules which form the scaffold within the cell to help cells to maintain their shape. Together with microtubules, the RanBP2 protein helps transport materials within cells. In neurons, it is likely that RanBP2 protein involved in the regulation of energy and maintenance of the blood brain barrier.

Have identified at least three missense mutations in the RANBP2 gene that increase the risk of developing acute necrotizing encephalopathy type 1. These mutations change amino acids in the RanBP2 protein, leading to the synthesis of a protein can not function normally, either due to altered shape or because it can not access the nuclear pore where it is needed. These genetic mutations do not cause health problems on their own and it is unclear how they are involved in the process by which a viral infection causes neurological damage. While individuals with acute necrotizing encephalopathy type 1 often have damage and lose their blood - brain barrier, the influence of RANBP2 gene mutations is unknown. It is believed that individuals who develop acute necrotizing encephalopathy type 1 produce an excess of cytokines in response to infection. Excessive cytokine causes a prolonged inflammation, although the role of altered protein RanBP2 this process is unknown. Inflammation is a normal immune response to injury and external agents such as viruses. However, excessive inflammation can damage many of the body's tissues. In addition, certain cytokines can be toxic to neurons when present in large quantities. It is suspected that the combination of protein and altered RanBP2 abnormal immune response plays a role in the susceptibility of individuals to recurrent episodes of acute necrotizing encephalopathy type 1. In people with acute necrotizing encephalopathy type 1, the virus is not found in nerve cells in the central nervous system, so it is likely that the immune response, rather than the infection itself, is responsible for neurological signs and symptoms.

The Influenza virus is most often found in people with acute necrotizing encephalopathy type 1; other viruses that are known to trigger this process include the human herpesvirus 6, coxsackievirus, and Enterovirus. In rare cases, it is implicated bacterium Mycoplasma pneumoniae. Some signs and symptoms of acute necrotizing encephalopathy type 1 have an identified mutation in the gene RANBP2. In these cases, the gene associated unknown.

This process is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to increase the risk of developing the process after infection. In most cases, an affected person inherits the mutation from one parent. Other cases are due to new mutations in the gene and occur in people with no history of disease in your family. Some people who have the RANBP2 altered gene never develop the disease, a situation known as reduced penetrance. It is estimated that an individual with a genetic mutation RANBP2 has a probability of 40 percent of developing acute necrotizing encephalopathy type 1 during their lifetime. Certain additional genetic or environmental factors likely play a role in whether an active infection signs and symptoms of this process. The health history of the individual, such as nutritional status and number of previous infections may also influence risk.

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with acute necrotizing encephalopathy type 1 by PCR amplification of complete exons RANBP2 gene, and subsequent sequencing.

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).