What is an Aganglionosis? Explain its genetics, treatment, signs and symptoms
It is defined as a disorder in which there is an increase in the size of colon which occurs due to the obstruction of bowel. It leads to the aganglionic section of bowel in which there are no normal enteric nerves. It starts at the anus and goes in the upwards direction. It is also known as the Hirsch sprungs disease. It is also known as the congenital aganglionic mega colon. The bowel which is affected is different in different individuals. In very few cases it is more than 30 cm.
What is the history of Aganglionosis?
It includes the name of disease after the physician of Danish named as an H Hirsch sprung. It was described first in the year 1886. It told us about the couple of infants who are no more and had a swollen bellies. The autopsies showed identical pictures which had a dilatation along with the hyper trophy of colon. It is the most important feature. This disorder is congenital and involves the colon. In this there is an absence of the nerve cells which are also known as the ganglion cells. It leads to the chronic constipation. The diagnosis of this disorder is mainly done with the help of barium enema. A rectal biopsy shows a lack of cells of the ganglion. It is a unique method of diagnosis.
The main treatment is mainly a pull through surgery. In this small portion of the colon have no nerve cells. They are pulled through the part that has no nerve cells. This is according to the National Digestive disease information clearing house. This disease was also considered to be a multi factorial when it came early in the scene. It was supposed to be caused by the nature as well as nurture. In the year 1993 and in the month of August there were couples of articles published by the independent groups in the nature article. It suggested that this disorder can be mapped to stretch of chromosome 10. The research also suggested that this disorder was caused by a single gene.
What is the genetics of Aganglionosis?
It includes the scientists in the year 2002 who stated that they have found a solution to this disorder. This research indicated that this disorder is mainly caused by the interaction between a couple of genes and encoded proteins. The chromosome 10 has a RET proto onco gene. It was identified as one of the gene which was involved. It also came to know that the dominant mutations can occur with the RET proto onco gene. In this there is a loss of function the protein it encodes and the protein which has to interact with the RET proto onco gene can lead to this disorder. It is referred as the EDNRB and is encoded by a gene which is present on the chromosome 13. There were other genes also which were identified by this disorder. The genes which were present on the chromosome 5 were known as GDNF. The genes which were present on the chromosome 20 were known as EDN3. The genes which were present on the chromosome 22 were known as SOX 10. The genes which were present on the chromosome 1 were known as NRTN. The genes which were present on the chromosome 2 were known as S1P1. The mode of inheritance of this disease is oligo genic. It refers that the two genes have the ability to interact and give rise to a disease. In order to have a disorder in the child the EDNRB which is encoded by a gene which is present on the chromosome 13 and RET proto onco gene with variations can lead to this disorder. The genes which we have discussed above have a vital role in the occurrence of this disorder. But the researchers are not able to locate the interaction between and their mechanism of EDNRB which is encoded by a gene which is present on the chromosome 13 and RET proto onco gene. The origin of this disease is controversial. There are syndromic cases of the disorder which cause due to the mutations which occur in PHOX 2B. It also includes other autonomic nervous system defects.
The RET coded proteins have the ability to help the cells of neural crest. They have the ability to become a ganglion cell. They can move to the digestive tract when the embryo develops. EDNRB which is encoded by a gene which is present on the chromosome 13 has the ability to code for proteins which connect the nerve cells to digestive tract. It means that the absence of certain nerve fibers is related to the couple of genes which have the ability to mutate so that the wrong proteins are formed. A research was published in the year 2004 which stated that there are 10 genes associated with this disorder. There are other studies which showed that the mutations in EDNRB which is encoded by a gene which is present on the chromosome 13 have a large impact on this disorder.
There was B Swain of Seattle in the children hospital which indicated that the most important gene which can lead to this disorder is RET. It has the ability to mutate in number of ways. It is linked with the Down syndrome. The Down syndrome is in combination with the RET. This disorder has 2 percent cases of the Down syndrome. The RET is involved in the cases of cancer of thyroid and neuro blastoma. These cases have been seen in this dis order with a greater frequency as compared to the rest of population. The RET also has the ability to control the movement of neural crest cells. It occurs via intestine in the fetus which is developing. There are mutations in the RET which can lead to this disorder and the cells travelling via colon stops when there occurs mutation. The severity of this disorder depends on the mutation of RET. The earlier it occurs more severe it becomes.
The researchers are not clear about the cause of this disorder. There was Dr. Swain who did the study in familial case and found that this disorder has autosomal dominant mode of transmission. In this the gene RET is more dominant. In few cases this doctor noticed that there was absence of the inheritance pattern. It is easy to treat this disorder but it is not easy to know about the cause of this disorder. Surgery is the most effective way to treat this disorder. It is stated by the national digestive diseases information clearing house. If this disorder is not treated it can lead to the development of enter colitis. In this case there is an inflammation of the small intestine and colon. It resulted in the death of couple of boys which suffered from this disorder. The part of the bowel which is non functional is used to removed with the help of surgery. It is helped to restore the function of bowel.
This disorder along with the hypo ganglion sis and gut dys motility is done with the autosomal inherited porphyrias. The children may require enzyme or testing of the DNA so that the disorder may not form or excrete porphyrins before the puberty.
What is the diagnosis of Aganglionosis?
It includes the child who has not passed the meconium. It occurs within 48 hours of the delivery. A suction biopsy is quite helpful in making a definite diagnosis which occurs in the distal narrow segment. Most of the babies pass the meconium within 24 hours and the next 10 percent pass within 48 hours.
What are the signs and symptoms of Aganglionosis?
It includes the incidence of 1 is to 5000 births. In this the ganglion cells are absent and mostly involve the males. Three fourth of the males have no cells in the recto sigmoid. A few of them have no cells in the colon. There is an enlarged section of the bowel which is done to and is found proximally. There is a narrow section which occurs distally. The ganglion cells are not present and it can lead to the persistent over stimulation of the nerves involving the affected areas. It causes the contraction and leads to the constipation, distension of the abdomen and a delayed passage of the meconium.
What is the treatment of Aganglionosis?
Surgery is the most effective way to treat this disorder. It is stated by the national digestive diseases information clearing house. If this disorder is not treated it can lead to the development of enter colitis. In this case there is an inflammation of the small intestine and colon. It is followed by the renastomosis. There are couples of steps which are required to achieve this goal. In the first step there is a process known as the colostomy. In this process there is cut in the large intestine and an opening is made through the abdomen. It allows the contents of bowl to be discharged into the bag. Later on one can go for a pull through procedure as the child weight, age and condition becomes ok.
The cause of this disorder was first discovered by an O Swenson. It was first done in the year 1948. There is a pull through procedure in which the colon is connected by a bowel to anus. The pull through procedure is quite helpful in the patients who are young and have this disorder. The original procedure was first described by Swenson but the pull through procedure has been changed a lot. There was an expert in the pull through procedure by Swain and he stated that there are 5 different types of a pull through procedure and are more or equal effective in the treatment of this disorder.
There are different procedures given by the Swenson, Duhamel and Boley. They are different from the Swain. The Swenson procedure has the ability to leave a small area of the diseased bowel. The Soave procedure has the ability to leave an outer wall of colon unchanged. The Boley procedure has the ability to leave a small modification of the procedure of Soave. The Duhamel procedure has the ability to leave a surgical stapler to connect the different types of bowel. There are no cells in the front of bowel. It leaves a healthy black as per Swain.
There is a current practice which is done to perform the procedure in which there is no colostomy. According to the pull through procedure it requires a colostomy. There is an increased awareness among the doctors and parents about this disorder. If the diagnosis is made early than the doctors can keep colon clean than a pull through procedure is done without a colostomy. Most of the patients with a pull through procedure live life normally. There are few patients who take laxatives for their rest of life. There are other treatment available for this few patients. A laxative or a diet rich in the fiber is given to the patients who have constipation. If there is no control than the stoma is required. One can also go for Malone. In this a tube is used to enter in the abdomen and goes via wall appendix to the colon. Bowel must be flushed once daily. There are children who are less than 6 years of age and do fine administration.
The involved portion of the lower intestine is restricted to the lower part of rectum. There are other surgical procedures like posterior rectal myectomy can be done.