RECURRENT FEVERS DUE TO GENETIC DISORDERS

Introduction:

Recent scientific research has shown that some rare diseases with recurrent fever are due to a genetic disorder. In many of these, other members of the family may also have recurrent fever.

• What does a genetic disorder mean?

A gene is changed as a result of an accident. This process is called 'mutation'. This mutation changes the function of the gene and can cause it to send wrong signals to the body, causing disease. Everyone has two copies of each gene. One is inherited from the mother and the other from the father. If this mutation is present in the mother and/or father, genetic transmission can occur in 2 different ways:

Recessive inheritance: Both mother and father carry the mutation in only one of their two genes. They do not have the disease, because there must be a mutation in both genes for the disease to occur. Only one in every four children of a family whose parents are carriers carries the risk of getting a mutation from both sides and becoming ill.

Dominant transmission: A single mutation is sufficient for the disease to occur. This In this case, one of the parents is sick and the risk of transmission to the child is two to one.

The mutation may not be present in the parents. The event that caused the mutation occurred during the pregnancy of the child. This situation is called de novo mutation. Theoretically, there is no risk for the other child in the family (or as much as for any other child), but the child carrying the disease will have a two-to-one risk, similar to that of dominant inheritance, in their own children.

• Hereditary relapsing fevers

The following diseases are included under this heading:

• Familial Mediterranean Fever (FMF) (See Familial Mediterranean Fever)
• Familial Hibernian fever = TNF Receptor associated Periodic Syndrome (TRAPS)
• Mevalonate Kinase-related Periodic Fever Syndrome (MAPS = hyper IgD Syndrome, HIDS)
• Chronic Inflammatory Neurological, Cutaneous, Articular Syndrome ( CINCA = NOMID)
• Muckle-Wells Syndrome (MWS) and Familial Cold Urticaria (FCU)
• Recurrent fevers whose hereditary nature has not been shown:
• Aphtha, Pharyngitis, Adenitis with Periodic Fever (PFAPA)

 

• What is TRAPS?


TRAPS (Periodic fever syndromes associated with tumor necrosis factor receptor 1), digestive system problems, red skin rashes, muscle aches with recurrent high fever lasting 2-3 weeks It is a group of dominantly inherited diseases that occur with swelling around the eyes. This disease has been described very recently.
TRAPS's course is quite benign, but14% of patients develop a serious kidney disease called amyloidosis.

• What is its frequency?

It is a very rare disease. Although its actual frequency is unknown, there are approximately 100 patients whose diagnosis has been confirmed so far. It affects girls and boys with equal frequency. Symptoms of the disease usually appear in late childhood or early adulthood.
The first cases were reported in families of Irish-Scottish origin, but later the disease was also described in French, Italian, Sephardic and Ashkenazi Jews, Armenians, Arabs and Moroccans.
The effect of seasons and climates on disease attacks has not been shown.

• Is it hereditary?

TRAPS dominant inheritance This means that more than one diseased individual can be seen in each generation of a family. The decrease in consanguineous marriages causes a decrease in such increased cases of disease within the family.
It has been shown that the gene responsible for TRAPS is located on chromosome 12 (12p13 region). This gene is located. The mutation leads to the formation of abnormal TNF receptors. As a result, these receptors cannot be released sufficiently in any inflammatory response in whichTNF plays a role. So far, 33 different mutations have been identified in this gene.

• Why did my child get this disease? Can its occurrence be prevented?

Your child has inherited this disease from a mother or father who carries the TNF Receptor gene mutation. Or a new mutation (de novo) occurred during pregnancy.
It is not possible to prevent the disease with our current knowledge.

• Is the disease contagious?

TRAPS microbial r is not a disease. It may occur only in genetically affected people.

• What are the main complaints and findings?

The main complaint lasts for about 2-3 weeks. It is an attack of fever accompanied by persistent shivering and severe muscle pain in the trunk and arms. Red and painful skin rashes may occur. These usually develop over painful skin and muscle areas.

Most patients complain of 'deep' cramp-like muscle pain that gradually increases in severity at the beginning of the attacks. These pains then move towards the extremities of the body and are followed by rashes. Generalized abdominal pain, nausea and vomiting are quite common. Although inflammation of the membrane of the eye (conjunctivitis) or swelling around the eye are characteristic findings for TRAPS, they may also be observed in some other conditions (such as allergies). p>

Unlike these typical findings, TRAPSmay sometimes occur with shorter or longer attacks. Chest pain may occur as a result of inflammation of the lungs or heart membrane.
Amyloidosis, the most severe complication of TRAPS, occurs in a small number of patients. In amyloidosis, increased amounts of protein begin to appear in the urine and kidney failure develops over time.

• Does the disease progress the same in every child?

TRAPS, the duration of attacks and the periods between attacks vary from patient to patient. Complaints and findings are not the same in every child. These changes may be due to genetic factors.

• How is the disease diagnosed?

The specialist physician determines TRAPS based on the symptoms of the disease and family history. is suspected. Some blood tests are useful during an attack. The diagnosis becomes certain if mutations can be shown through genetic tests.

In the differential diagnosis, it is necessary to consider other diseases that cause recurrent fever (especially familial Mediterranean fever-FMF, and hyper IgD syndrome).

• What is the treatment?

Today, there is no definitive treatment for the disease. During attacks, anti-inflammatory drugs can help by reducing symptoms. Short-term high-dose corticosteroids are usually effective, but long-term use requires attention to side effects. cli. Drugs that block TNF have been shown to be effective if they can be given at the beginning of an attack.

• How long should treatment be continued?

Treatment is only used for attacks. He is angry with. Unfortunately, there is no medicine to prevent attacks from coming.

• How long does the disease last?

TRAPS lasts a lifetime. Attacks recur at indeterminate intervals.

• What is the long-term development of TRAPS?

The worst possibility is amyloidosis, which is seen in a small number of patients. is its development. It is difficult to calculate this risk because the development of amyloidosis depends on some environmental factors as well as genetics. Amyloidosis often leads to kidney failure. A method that will prevent the development of amyloidosis is not known today.

• Is it possible to get rid of the disease completely?

The existence of such a possibility is not yet known. With further studies, perhaps long-term remission can be achieved if the causes that trigger the attacks can be identified and their warnings can be prevented. >HIDS)

• What kind of disease is it?

Mevalonate kinase-associated periodic fever syndrome (MAPS) It is a hereditary disease. Patients complain of recurrent high fever and accompanying skin rashes, swollen lymph nodes in the neck, abdominal pain, vomiting and diarrhea. The most severe form of MAPS is called mevalonic aciduria. Children suffering from this congenital form have fever attacks as well as developmental delay and neurological damage. The mildest form of MAPS is HyperIgD and periodic fever syndrome (HIDS), which we discuss here. This name was given because most patients have high levels of a protein called IgD in their blood.

• How common is it?

MAPS It is a rare disease. About 200 patients have been reported so far. Most of these have the mild formHIDS. This form is seen especially in Western Europe (Netherlands and France). Although rare, MAPS strong> is found in all societies. Boys and girls get sick with equal frequency. Symptoms of the disease usually appear in the first years of life.

• What are the causes of the disease?

MAPSin metabolism It occurs as a result of an internal disorder. The reason for this is calisal. The gene affected in MAPS is calledMVKgene. Each gene is equipped with the information necessary to make a specific protein. TheMVK gene also contains information about the production of mevalonate kinase protein. Mevalonate kinase is an enzyme. Enzymes are proteins that facilitate many chemical reactions that occur in our body. The chemical reaction here is the transformation of mevalonate into phosphomevalonate. This is the first step in the reactions required to form a number of important molecules (such as cholesterol).
Enzymes that are genetically different from normal affect our body's metabolism and are therefore called MAPS The diseases are known as internal metabolic disorders. The severity of the disease is proportional to mevalonate kinase deficiency. In mild forms, the activity of the (HIDS) enzyme is 1 to 10% of normal.

MAPS autoinflammatory ( It is a disease caused by inflammation caused by the organism itself. Despite all the research, it has not been understood why mevalonate kinase deficiency causes fever and inflammation. The symptoms that occur during attacks are similar to the general inflammation seen when the child's body is fighting a very serious microbe. In this situation, fever, loss of appetite, fatigue, as well as an increase in the number of white blood cells, sedimentation rate and CRP tests are observed. Since these symptoms are not caused by an external microbe, MAPS can be defined as an autoinflammatory disease.

It is not known why a constantly existing genetic disorder causes attacks from time to time. These attacks may occur spontaneously or may be triggered by psychological stress, other infections, or, typically, vaccinations. In girls, menstrual periods can also cause attacks. The frequency and severity of attacks decrease during pregnancy.

• Is it hereditary?

As with many human genes, Every body cell is affected by the MVKgene.

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