The Role of Genetics Mutations in Gene RANBP2 in Acute Necrotizing Encephalopathy Type 1 Syndrome

Asadi S, Jamali M, Arzeloo SN and Habashizadeh M

Published on: 2019-07-15

Abstract

ANE1 syndrome usually appears in infancy or early childhood, although some people do not develop this condition until adolescence or adolescence. The ANE1 syndrome is caused by the mutant of the RANBP2 gene, which is based on the long arm of chromosome number 2 as 2q13. Influenza is the most common viral infection seen in people with ANE1 syndrome. Some people who have changed the RANBP2 gene have never developed the condition of the syndrome, a condition known as impaired penetration.

Keywords

Acute necrotizing encephalopathy type 1 syndrome; Cerebrovascular disease; Edema; Hemorrhage; Necrosis; RANBP2 gene

Introduction

Generalizations of acute necrotizing encephalopathy type 1 syndrome (ANE1)

Acute necrotizing encephalopathy type 1 syndrome, also known as acute infectious encephalopathy 3 or IIAE3, is a rare case of cerebrovascular disease (encephalopathy) that occurs after a viral infection such as an influenza virus [1].

Signs and symptoms of acute necrotizing encephalopathy type 1 syndrome (ANE1)

ANE1 syndrome usually appears in infancy or early childhood, although some people do not develop this condition until adolescence or adolescence. People with this condition usually show signs of infection for a few days, such as fever, cough, congestion, vomiting and diarrhea. Following symptoms of influenza, people with this syndrome experience neurological problems such as seizures, hallucinations, lack of coordination of movements (ataxia), or poor muscle tone. Eventually, most people suffer from coma, which usually lasts a few weeks. This condition is described as "acute" because the parts of the disease are limited to time [2] (Figure 1).

Figure 1: Schematic of anatomy of the human brain.

People with ANE1 syndrome cause damage in certain areas of the brain. With the progression of the disease, these areas of the brain, swelling (edema), bleeding (hemorrhage) and then tissue death (necrosis) are caused. Progressive damage to the brain and loss of tissue causes encephalopathy [2]. Approximately one-third of people with ANE1 syndrome suffer from mental decline. Of those who survived, about half of permanent brain damage is due to tissue necrosis, which leads to walking disorders, speech impairment and other skills. Over time, many of these skills may be regained, but permanent loss of permanent brain tissue. Other people who survived the disease are fully recovered [2].

It is estimated that half of the people with ANE1 syndrome are susceptible to recurrence of the disease and have another infection that results in decreased function of the nervous system. Some people may have multiple parts of their illness throughout their lives. The function of the brain becomes worse after each part, because the brain tissue is more damaged [2] (Figure 2-4).

Figure 2: Schematic view of chromosome number 2, in which the RANBP2 gene is located in the long arm of this chromosome 2q13.

Etiology of acute necrotizing encephalopathy type 1 syndrome (ANE1)

The ANE1 syndrome is caused by the mutant of the RANBP2 gene, which is based on the long arm of chromosome number 2 as 2q13. The RANBP2 gene provides instructions for protein synthesis that interacts with a protein complex known as nuclear fusion. Channel nuclear pores, which allow molecules to be transmitted inside and outside the cell nucleus. The RANBP2 protein helps to transport proteins and other molecules through the nucleus pores, and helps to change the proteins that go into and out of the nucleus. RANBP2 proteins, in addition to its functions in nuclear pores, also play a role in cell division, helping to transport materials in cells [3].

Figure 3: Schematic of mycoplasma pneumonia bacteria.

RANBP2 gene mutations associated with ANE1 syndrome produce a protein that cannot function normally due to its modified form or cannot go to the nucleus pore where it is needed. These mutations do not cause health problems on their own and it is not clear how these mutations are involved in the process by which the viral infection causes neurological problems. Researchers believe that long-term inflammation in response to the infection may be involved in the spread of ANE1 syndrome, although the role of the RANBP2 protein altered in this process is unknown. Inflammation is the response of the natural nervous system to damage and external invasions (such as viruses). However, excessive inflammation can damage the tissues of the body. In addition, some inflammatory proteins can be poisonous when exposed to large amounts of nerve cells. It is suspected that the combination of RANBP2 protein has been altered and abnormal immune responses play an important role in sensitizing individuals to frequent episodes of ANE1 syndrome. In people with ANE1, the virus does not appear in the brain or spinal cord (central nervous system), so the immune response is likely to be due to neurological signs and symptoms rather than infection [3] (Figure 5-6).

Figure 4: Schematic of the mechanism of RANBP2 gene function in the death and survival of the neuron (neuron).

Influenza is the most common viral infection seen in people with ANE1 syndrome. Other viruses that lead to this disease include the human-herpes viruses 6 of the Koksaki virus and enteroviruses. In rare cases, mycoplasma pneumoniae is also involved in this syndrome. Since the signs and symptoms of the ANE1 syndrome are not significantly different among different infections, it is likely that the type of infection is less likely to occur than an infection to develop the disease [3].

Figure 5: Schematic of the building block of RANBP2 protein.

Figure 6: Images of symptoms of human infection with mycoplasma pneumonia.

Some people with signs and symptoms of the ANE1 syndrome do not have any type of mutation in the RANBP2 gene. In these cases, the gene that interferes with the syndrome is unknown [3]. The ANE1 syndrome follows the dominant autosomal inheritance pattern. Therefore, to produce this syndrome, a copy of the mutated gene RANBP2 (parent or parent) is required and the chance of having a child with this syndrome in the dominant autosomal state is 50% for each possible pregnancy [3]. Some people who have changed the RANBP2 gene have never developed the condition of the syndrome, a condition known as impaired penetration. It is estimated that a person with a mutation of the RANBP2 gene is likely to have an exposure of 40% to the lifetime of ANE1 syndrome. Other genetic or environmental factors may play a role and explain whether the infection causes the symptoms and symptoms of the disease. A person's health history, such as the nutritional status and the number of previous infections, may also affect the risk of the disease [3].

The frequency of acute necrotizing encephalopathy type 1 syndrome (ANE1)

The ANE1 syndrome is a rare genetic disorder whose frequency is not known in the world. At least 59 cases of this syndrome have been reported in medical literature from around the world [4] (Figure 7-9).

Figure 7: Radiographic images of brain disorders in ANE1 syndrome.

Diagnosis of acute necrotizing encephalopathy type 1 syndrome (ANE1)

ANE1 syndrome is detectable based on clinical and physical findings of the patients and some pathological tests. The most accurate method for detecting this syndrome is the molecular genetic testing of the RANBP2 gene to investigate the presence of possible mutations [5].

Figure 8: Schematic view of the dominant autosomal inheritance pattern that the ANE1 syndrome follows from this pattern.

Therapeutic routes of acute necrotizing encephalopathy type 1 syndrome (ANE1)

The treatment and management strategy for ANE1 syndrome is symptomatic and supportive. Treatment may be done by a team of experts including an infectious disease specialist, respiratory specialist, neurologist, physicians and other healthcare professionals. There is no effective treatment for this syndrome, and all clinical measures are needed to reduce the suffering of the sufferers. Genetic counseling is also important for all parents who want a healthy baby [6].

Figure 9: Radiological images of the viral infection of the influenza virus in the brain (A-H), the microscopic picture of mycoplasma pneumonia (middle image), and the rheumatologic image of mycoplasma pneumonia respiratory tract infection (Fig. A-B).

Discussion and Conclusion

Neurologic complications of influenza have been well described in the literature and date back to the diagnosis of encephalitis lethargica during the 1918 influenza pandemic. Neurologic manifestations of influenza are now known to include encephalitis, acute disseminated encephalomyelitis, Guillain-Barre syndrome, transverse myelitis, and acute necrotizing encephalopathy (ANE). Reports of ANE began surfacing from Japan during the influenza epidemics of the mid-and late 1990. Influenza-associated central nervous system (CNS) dysfunction has also been reported, although infrequently, in Europe and the United States. Other infections associated with ANE include human herpesvirus-6 infection, measles, parainfluenza infection, and mycoplasma infection. People with ANE1 syndrome cause damage in certain areas of the brain. With the progression of the disease, these areas of the brain, swelling (edema), bleeding (hemorrhage) and then tissue death (necrosis) are caused. Progressive damage to the brain and loss of tissue causes encephalopathy. There is no effective treatment for this syndrome, and all clinical measures are needed to reduce the suffering of the sufferers [1-6].

References