MUTYH-associated polyposis is closely related to adenomatous familial polyposis and is caused by a genetic mutation. Patients suffer from multiple colon polyps with risk of degeneration. Regular colonoscopies are mandatory.
What is MUTYH-associated polyposis?
Polyposis is polyp disease in hollow organs. Polyps are outpouchings of the mucosa that occur more frequently in the gastrointestinal tract, among other places, and in this case are referred to as polyposis gastrointestinalis. Especially in the context of polyposis gastrointestinalis there are different diseases with genetic and hereditary basis. One of them is autosomal dominant hereditary MUTYH-associated polyposis, also known as MAP or MHY associated polyposi. The disease was not discovered as a distinct inherited disorder until 2002. It behaves as a clinically attenuated variant of familial adenomatous polyposis (FAP). For this reason, researchers have assumed since its discovery that the generalized course of the disease resembles AFAP. In addition, patients with mild course of adenomatous familial polyposis are now diagnosed with MAP in up to 20 percent of all cases. Thus, MUTYH-associated polyposis can be broadly considered as the most favorable subvariant or close relative of adenomatous familial polyposis. According to studies, approximately one percent of the population are carriers of the disease.
Causes
The cause of MUTYH-associated polyposis lies in the genes. More specifically, it is a mutation in the MUTYH gene, which is located on chromosome 1 in gene locus 1p34.3-p32.1. The associated base pairs 45,464,007 to 45,475,152 carry 16 coded exons. The parent MUTYH gene is involved in the production of a DNA repairing protein in a healthy organism. This is the so-called MUTYH glycosylase, which monitors base pair formation. Physiologically, the base pairs of the gene occur in two different forms and thus consist of adenine with thymine or guanine with cytosine. Upon oxidation, the base pair partners shift. Guanine can thus form a pair with adenine, for example. In healthy organisms, the DNA repairing protein recognizes this event and repairs the error. In the case of a mutation in the MUTYH gene, MUTYH glycosylase loses its proper form and can no longer adequately perform its tasks. The mode of inheritance of MUTYH-associated polyposis is autosomal recessive. Siblings of a patient thus have a 25 percent risk of inheriting the polyposis. Children of a patient will carry the inherited disease in any case.
Symptoms, complaints, and signs
Patients with MUTYH-associated polyposis suffer from polyps of the colon. The polyps may occur in clusters of up to 100. However, in some cases, only ten polyps have been reported. Associated with polyps of the colon are accompanying symptoms such as bleeding, flatulence, colic, and pain in the rectal area. In addition, constipation, diarrhea, and severe weight loss are common. Despite the sometimes considerable number of colon polyps, the disease is thought to be milder in its course than familial adenomatous polyposis coli. Regardless, hyperplastic or serrated adenomas are frequently found among the multiple polyps. Thus, an increased risk of cancer is associated with the hereditary disease. The median age for colon carcinoma is about 50 years for carriers of the disease. The carcinomas preferentially form in the proximal portion of the colon. Benign bone tumors in the sense of osteomas have also been observed more frequently in the context of MUTYH-associated polyposis.
Diagnosis and disease course
In most cases, the diagnosis of MUTYH-associated polyposis is made at an age older than 50 years. In most cases, affected individuals seek medical attention because of bleeding or persistent pain in the rectal area. As part of the diagnosis, an endoscopy including biopsy of the polyps is usually performed. A human genetic examination can round off the diagnosis. This procedure is indicated primarily for cases in which FAP has been ruled out despite the presence of many colonic polyps. As part of the human genetic analysis, a complete sequencing of the MUTYH gene is performed.Although patients with MUTYH-associated polyposis are also at increased risk of colorectal cancer, their prognosis is far more favorable compared with patients with FAP.
Complications
As a result of this disease, affected individuals primarily suffer from discomfort in the bowel. This results in the formation of so-called polyps, which eventually lead to colic, flatulence, and pain in the area of the intestine and stomach. It is not uncommon for those affected to also suffer from diarrhea or constipation, resulting in a greatly reduced quality of life. Furthermore, permanent complaints of the stomach and intestines can lead to psychological problems or depression. The risk of cancer is also significantly increased by this disease, so that patients are dependent on various preventive examinations. Not sailing the patients take less food by this illness, so that it comes to deficiency symptoms or to an underweight. Above all, the risk of colorectal cancer increases enormously as a result of this disease. Treatment is usually carried out with the aid of medication. No particular complications occur. Through various regular examinations and controls, further diseases can be avoided or detected at an early stage. If the affected person suffers from underweight or deficiency, the missing nutrients must be administered by infusion.
When should one go to the doctor?
Irregularities in the bowel should be observed by the affected person. If they persist for several days or increase in severity, they should be referred to a physician. If flatulence, constipation or diarrhea occur, a visit to the doctor is advised. If there are bowel sounds, a feeling of pressure or pain in the abdomen, there is a disorder that needs medical attention so that no further complications follow. A loss of appetite, an unwanted decrease in body weight, and a feeling of internal dryness are signs where action is needed. A decrease in available strength, sleep disturbances or a general feeling of illness should be examined and treated. If the daily professional and private obligations can no longer be fulfilled, the affected person should seek the help of a doctor. If there is bleeding during bowel movements, itching or open sores on the anus, a visit to the doctor is advisable. Pathogens can penetrate into the organism and lead to further diseases. In addition, sterile wound care is necessary to prevent blood poisoning. A doctor should be consulted if there are skin changes, a burning sensation at the anus, fever, malaise or internal weakness.
Treatment and therapy
Causative therapy is not available for patients with MAP because the disease is genetic and results from DNA damage. Substantial advances in gene therapy have now been observed, so that a gene therapy-causal therapeutic approach cannot be ruled out within the next few decades. However, since gene therapy approaches are not yet in the clinical phase, patients with MUTYH-associated polyposis have so far been treated exclusively symptomatically. Symptomatic treatment focuses less on actual therapy than on regular control. Control examinations in close-meshed intervals are obligatory because of the increased cancer risk and should take place at the latest from the age of 30. Biopsies are taken from hyperplastic or otherwise conspicuous polyps as part of the preventive examinations. Particularly conspicuous representatives are removed by resection, if necessary, in order to contain the risk of degeneration. In addition to check-ups, patients with the disease are offered symptomatic pain therapy, which is usually equivalent to drug treatment. If malnutrition occurs due to persistent diarrhea, intravenous infusions are used to compensate for the deficiency in question.
Outlook and prognosis
MUTYH-associated polyposis (MAP) obviously increases the risk of developing colorectal cancer due to genetic factors. Therefore, the prognosis is not so positive in the long term. Therefore, accurate and comprehensive diagnosis is important first to clearly distinguish MUTYH-associated polyposis as such from similar hereditary gastrointestinal polyposis syndromes.Secondly, adequate therapy and long-term monitoring of colon polyps through regular examinations of the intestinal tract are useful. The risk of degeneration in this type of colon polyp is significantly higher than in other intestinal diseases. MUTYH-associated polyposis requires regular colonoscopies for this reason. This allows any colon cancer that may develop to be detected as early as possible. Compared with so-called FAP polyposis, the prognosis for people with confirmed MUTYH-associated polyposis is significantly better. But the overall outlook is still poor. In this respect, it can be said that MUTYH-associated polyposis may indeed carry long-term colorectal cancer risks. However, these risks can be minimized by regular colonoscopies and genetic detection of polyp type. Early detection in this case provides a safe tool to promote a cure if colorectal cancer is diagnosed. It is also important that patients with MUTYH-associated polyposis pay attention to their nutritional levels. With constant bowel symptoms, nutrient deficiencies of concern easily develop. Infusion treatments may be necessary to ensure nutrient adequacy.
Prevention
Molecular genetic analysis is a preventive step in the context of MAP. In particular, people with a corresponding family history learn through the analyses whether they are homozygous carriers of the MUTYH gene mutation. If so, regular colonoscopies starting at age 30 years serve to prevent cancer.
Follow-up
Because of the disease, those affected suffer from severe complications and serious symptoms. Therefore, in this disease, a doctor must be consulted at the first symptoms and signs, so that there is no further worsening of symptoms. If the disease is not treated, the worst case scenario can lead to the death of the affected person. Those affected primarily suffer from severe abdominal discomfort. They experience diarrhea, constipation and generally severe pain in the abdomen. Likewise, many patients suffer from flatulence and even bloody diarrhea. The permanent abdominal discomfort can also cause a severe loss of weight. The risk of cancer also increases due to the discomfort, and many patients therefore develop colon cancer. The symptoms themselves can lead to depression or other severe psychological upsets in some sufferers, so that they are also dependent on psychological treatment. The further course of the disease depends to a large extent on the exact severity of the symptoms. In this case, the life expectancy of the affected person may also be reduced due to the disease.
What you can do yourself
Patients with MUTYH-associated polyposis suffer from unpleasant symptoms due to the disease of the colon, which reduce the quality of life. In their own interest, those affected regularly visit various specialists and undergo the preventive examinations offered in order to diagnose any cancers in time. Due to the uncertainty about the course of the disease as well as the symptoms themselves, some patients develop anxiety disorders or even depression. It is then urgent to consult a psychologist. The psychotherapist helps the patient cope with the physical illness and strengthens mental stability. If the doctor prescribes medication, the affected person must take it exactly according to the doctor’s orders. Patients often suffer from colic, diarrhea or constipation, which also have a negative impact on everyday life and make it difficult to participate in social life. Therefore, it is urgently indicated to consult a medical nutritionist. This person will develop an individual diet plan for the patient to reduce the symptoms and ensure the often impaired supply of nutrients. It is also helpful if those affected refrain from smoking and drinking alcoholic beverages. This saves the organism from having to process the corresponding toxins and, at best, has a beneficial effect on the course of the disease.
