Hirschsprung Disease - Clinical information

Hirschsprung disease:

Frequently asked questions: (Note:  Many words are defined in our Glossary of medical terms)
What is Hirschsprung disease? A birth defect where the enteric nervous system is missing from the end of the bowel.  The part of the bowel missing nerve cells does not work properly.
What are the symptoms of Hirschsprung disease?  Delayed passage of meconium (> 24 hours from birth), neonatal bowel obstruction (abdominal distension, green or yellow vomiting), constipation that does not respond to oral medicines, poor growth, and sometimes loose bowel movements with blood and accompanying fever.
How common is Hirschsprung disease?  About 1:5000 children born in the United States has Hirschsprung disease.  Rates vary around the world, but range from about 1:1000 to 1:10,000.  In contrast, about 1:4 (25%) of healthy children have problems with constipation.  The low frequency of Hirschsprung disease means that most children with constipation do not have Hirschsprung disease.  Furthermore, even if your pediatrician cares for 5000 children, they are unlikely to have more than one other child that they care for with Hirschsprung disease.  For this reason, most children with Hirschsprung disease need to see a pediatric gastroenterologist or pediatric surgeon in addition to their pediatrician.
How is Hirschsprung disease diagnosed?  Diagnosis requires rectal biopsy.  This is a simple low risk procedure, but you will need to see a pediatric gastroenterologist or pediatric surgeon to have this test done.  If nerve cells are present in the biopsy, then your baby does not have Hirschsprung disease.  Sometimes a specialized X-ray test called a contrast enema (often a barium enema) is performed to look for a "transition zone" that might indicate Hirschsprung disease, and to exclude other problems.  The Contrast enema may miss Hirschsprung disease 10-15% of the time, so a normal X-ray does not exclude Hirschsprung disease.  Some physicians perform anorectal manometry as a screening test for Hirschsprung disease, but biopsy is still needed for definitive diagnosis.
How is Hirschsprung disease treated?  The most important treatment is surgery to remove the part of the end of the bowel where the enteric nervous system is missing.  During the operation, the surgeon will identify by biopsy the part of the bowel that is missing nerve cells (i.e. aganglionic bowel) and the region where nerve cells are present.  In a "pull through" procedure, after removing the aganglionic bowel, the part of the bowel that contains nerve cells is connected to the anal opening so stool is passed in the usual way.  In some cases an "ostomy" is created to connect the end of the bowel to the front of the abdomen.  In most cases, the ostomy is temporary, but in children with long segment disease the ostomy may be permanent.
How much bowel is removed for Hirschsprung disease surgery? Most people (about 80%) who have Hirschsprung disease are only missing nerve cells at the very end of the colon.  However, the abnormal region may extend from the rectum for only a few inches or may extend much further into the proximal bowel. A small percentage of people with Hirschsprung disease are missing nerve cells throughout the colon, and some children even have aganglionosis extending into the small bowel.  Total intestinal aganglionosis (i.e., no nerve cells anywhere in the bowel) may also occur but is very rare. 
Is surgery necessary?  Yes.  Before surgery was developed to treat Hirschsprung disease, death rates from this disease were very high.  Surgery improves growth, reduces problems with abdominal distension and constipation and dramatically reduces the risk of death.
Is surgery a cure? No.  Although surgery makes children with Hirschsprung disease much better, many children (35-55%) continue to have some problems after surgery.  The most common problem is called enterocolitis.  These problems tend to become less frequent over time.
Does removing aganglionic bowel cause problems (i.e., isn't the bowel needed for life)? The colon's primary job is to absorb water from stool into the bloodstream.  Removal of a short segment of the end of the colon does not typically cause problems.  If the whole colon is removed, stool will be looser than normal.  This can be a particular problem in young children, but adults without a colon usually appear healthy. If a large section of the colon is removed, water and salt losses will be higher than normal, especially with an infectious diarrheal illness. If aganglionosis extends into the small bowel, there may be even more serious problems with water, nutrient and vitamin absorption.  This problem is called "short bowel syndrome".
What is enterocolitis?  Enterocolitis is a potentially dangerous problem for children with Hirschsprung disease.  Symptoms may worsen over the course of hours and include "explosive", foul smelling or bloody diarrhea, abdominal distension, lethargy and fever.  If a rectal exam is performed there may also be an "explosive" release of gas or stool.  In some cases of enterocolitis, bacteria can enter the blood stream from the bowel to cause sepsis, a problem that can be fatal. 
What is the treatment for enterocolitis?  The most important treatment is rectal dilation (e.g., by rectal exam) and/or rectal irrigation.  This results in the release of intestinal contents under pressure and reduces the risk of blood stream infection.  In many cases, antibiotics are also used to treat or to prevent enterocolitis.  Metronidazole (Flagyl) is the most commonly used antibiotic in our institution.
What can be done to prevent enterocolitis?  Surgery reduces, but does not eliminate the risk of enterocolitis.  For children who have enterocolitis after surgery (a common problem), rectal irrigations and Metronidazole, along with rectal dilation, can be effective treatment.  Occasionally additional surgery is needed in children with frequent enterocolitis unresponsive to these approaches.
What are current death rates in children with Hirschsprung disease? About 5% of children with Hirschsprung disease still die of this disorder, typically as a result of enterocolitis.  Risk of death is dramatically reduced once the disease is recognized and treated.  Most people with Hirschsprung disease have normal life expectancy after treatment.
Are people born with Hirschsprung disease or does the disease begin after birth?  Because enteric nervous system precursors migrate through the bowel to form the ENS during the first trimester of pregnancy, Hirschsprung's is a disease of early prenatal human development. 
How old are people when diagnosed with Hirschsprung disease?  Some children have symptoms on the day they are born and the diagnosis is made within a week or two of birth.  About 2/3 children are diagnosed by 6 months of age.  It is not uncommon to diagnose Hirschsprung disease in older children, and some individuals are not diagnosed until they are adults, but this is less common.
What causes Hirschsprung disease?  In most cases, individuals with Hirschsprung disease have underlying problems with their DNA that predispose to disease.  This means that Hirschsprung disease is a genetic disease and the risk of disease is greatly increased in close family members of affected individuals.  The genetics of Hirschsprung disease are complicated and are summarized here Ongoing studies in model systems suggest that some environmental factors or maternal health issues may also affect the risk of Hirschsprung disease in children.  New studies in our laboratory are directed at identifying these non-genetic risk factors with the goal of reducing Hirschsprung disease occurrence.  You can help by participating in our human research studies.
 
Are other medical problems associated with Hirschsprung disease?  Yes. Many people with Hirschsprung disease have other medical problems (described here), but most affected individuals are otherwise healthy. 
What should I do to find out if my child has Hirschsprung disease?  First talk with your pediatrician.  If they think more evaluation is needed, you will be referred to a pediatric gastroenterologist or a pediatric surgeon to determine if your child needs evaluation for Hirschsprung disease, or a different diagnostic or management strategy.
What is the recurrence risk for Hirschsprung disease in families?  Because there are important genetic risk factors for Hirschsprung disease, parents who have one affected child are much more likely to have another child with this disorder.  Risk of Hirscshprung disease in boys is also much higher than in girls (5:1 male to female ratio in short segment Hirschsprung disease; 1.8:1 male to female ratio in long segment disease).  Recurrence risk (assuming the same parents) can be estimated without genetic testing as follows (modified based on this manuscript by Amiel et. al.):
General population Hirschsprung disease risk:  1:5000 children.
Recurrence rate within families varies from 1% to 33% for subsequent pregnancies as follows:
If first child is male and has short segment Hirschsprung: 5% for male siblings, 1% for female siblings.
If first child is female and has short segment Hirschspung: 5% for male siblings, 3% for female siblings.
If first child is male and has long segment Hirschsprung: 17% for male siblings, 13% for female siblings.
If first child is female and has long segment Hirschsprung: 33% for male siblings, 9% for female siblings.
Where can I get additional information about Hirschsprung disease?  Our favorite website providing information about Hirschsprung disease is hosted by the National Institute of Health (NIH).  The NIH is the primary supporter of medical research in the United States.  If you want more research done on Hirschsprung disease and other serious medical problems to find new ways to treat, cure or prevent these disorders, please write your congressional representatives and ask them to support medical research and the NIH.  At current federal funding levels only approximately 1 out of 10 grants submitted to the NIH is funded (10%) because of limited NIH resources.  You can find your representatives by entering your zip code into the search box at the top of the Congress.org web page.  They need to hear from you.

What if I still need more information about Hirschsprung disease?  Please send me an heuckerothr [at] email.chop.edu (email).  Our goal is to provide you with information and resources you need.  Your questions may spur modifications of this website.

What if I want to help with Hirschsprung disease research?  We have an active research study to learn more about what causes Hirschsprung disease and how it might be prevented.  You can participate in our study or may help in other ways.

Are there other types of enteric nervous system disease?  Because the enteric nervous system controls most aspects of intestinal activity, defects in ENS development or function are a common cause of human morbidity (i.e. suffering).  Serious problems with the ENS occur in Hirschsprung disease (see above) and in some cases of intestinal pseudo-obstruction syndrome (a rare disorder).  Defects in intestinal motility, however, occur in about 15% of the adult population as part of "Irritable bowel syndrome (IBS)".  It is reasonable to assume that at least some cases of IBS are a result of abnormal ENS function.  The enteric nervous system can also be damaged in some other diseases including diabetes.