What is Hirschsprung Disease?
Hirschsprung disease (HD) is a birth defect that involves missing nerve cells from certain parts of the intestines. It results in issues with moving stool through the intestines. The nerve cells are typically absent from the submucosa layer (the second layer of the intestine wall) and the muscular layer of the last part of the rectum. The extent of this can differ from person to person. It’s a fairly rare disorder, ranging from 1 to 1.63 out of 10,000 babies born.
In the past, this condition was often fatal, but thanks to surgical treatment, the mortality rate has dropped to about 3% in developed countries. HD mostly affects newborns and its symptoms aren’t always clear-cut. Some common signs include chronic constipation and intestinal blockage. Doctors diagnose it by examining tissue samples from the rectum under a microscope.
What Causes Hirschsprung Disease?
Hirschsprung disease happens when there’s a disruption in the process of cells transforming and migrating within the part of the nervous system that belongs to the intestines, all of which is controlled by a gene known as RET. Simply put, this condition results in the absence of specific types of cells in nerve clusters. This leads to the overworking of the intestines, causing the continuous release of a chemical called acetylcholine, which keeps the muscles in the affected part of the colon constantly contracted. This, in turn, causes other healthy parts of the colon to widen.
The inheritance of Hirschsprung disease is quite complicated, involving multiple genes. It doesn’t always show symptoms, can vary greatly, and is affected by the sex of the individual. The main gene involved is called RET and is found to be mutated in around 35% of cases where the disease shows up without a family history and 49% of cases where there’s a family history. Changes in the RET gene can occur in any one of its 21 parts, and more than 100 different types of changes have been identified.
Other genes that play a role in causing Hirschsprung disease show up in only 5 to 10% of cases. This includes the genes for RET’s partner molecules: the glial cell-derived neurotrophic factor (GDNF), endothelin-3, endothelin receptor B (EDNRB), and the SOX10 and PHOX2B genes.
Risk Factors and Frequency for Hirschsprung Disease
Hirschsprung’s disease (HD) is a disorder present from birth. It occurs in 1 out of every 5000 newborns and is more commonly seen in males with a ratio of 4:1. However, there are exceptions to this, especially in cases where the disease affects a large part of the colon.
- Most of the time, this disease is identified in newborns. About 65% of those diagnosed are less than a month old.
- About 95% are diagnosed within their first year.
- While it is seldom detected during adulthood, it has been diagnosed in people as old as 74.
Signs and Symptoms of Hirschsprung Disease
When diagnosing Hirschsprung’s disease (HD), a condition that can cause newborn babies to have bowel obstructions, doctors look out for several symptoms. These can include:
- Unusual amount of amniotic fluid around the baby while the mother is still pregnant (a condition called polyhydramnios)
- Constant vomiting, especially if the vomit is greenish (bilious emesis)
- Difficulty with bowel movements (obstipation), which might be indicated by the baby not passing the first stool (meconium) during the first 48 hours after birth
- Swelling of the baby’s belly (abdominal distention)
A history of obstruction in the large intestine, which blocks the path of stool, can occur anytime from birth till adulthood. The baby not passing meconium in the first 48 hours of life can suggest a diagnosis of Hirschsprung’s disease as this happens with up to 90% of affected patients. However, delayed passage of meconium can also happen in healthy individuals, approximately 40% of the time.
Other signs to watch out for are Hirschsprung’s associated enterocolitis (HAEC), which is an infection of the colon that can lead to serious complications, frequent constipation and a belly that is soft and looks swollen. There have also been cases where Hirschsprung’s disease is associated with genetic problems like Trisomy 21 (Down syndrome) and Waardenburg syndrome, which affects the color of a person’s hair, skin, and eyes.
Testing for Hirschsprung Disease
Hirschsprung’s disease (HD) can generally be diagnosed by finding absence of certain nerve cells, called ganglion cells, in a portion of the bowel tissue. However, making a definitive diagnosis based on this method can sometimes face hurdles. These hurdles might include a lack of pathologists (doctors who study disease by examining cells and tissue) experienced with these cases, poor quality or disorientation of the submitted tissue sample, or the presence of normal immature ganglion cells in newborns.
A key part of the evaluation process for Hirschsprung’s disease is examining the rectal tissue samples taken from the patient using specific staining methods, such as acetylcholinesterase (AChE) which tells pathologists whether certain cells are present or not. In addition, traditional staining methods (like H and E) are also important. Sometimes, tissue sections that have been rapidly frozen (fresh frozen section tissues) might be assessed using the AChE method.
Moving on to other diagnostic methods, anorectal manometry and contrast enema are also used to help confirm the diagnosis of Hirschsprung’s disease. Anorectal manometry is a test that measures changes in pressure in the rectum and anal canal, and it works on the premise that a certain reflex in the rectum and anal canal (recto-anal inhibitory reflex or RAIR) is always present in healthy newborns. An absence of this reflex could indicate Hirschsprung’s disease.
Moreover, a contrast enema is a test that uses a contrast medium introduced into the bowel to visualize the bowel on an x-ray. Certain features like a transition zone, reversal of recto-sigmoid ratio, mucosal irregularity, irregular contraction, and contrast that stays in the body for more than 24 hours are indicators of Hirschsprung’s disease when seen on a contrast enema.
Treatment Options for Hirschsprung Disease
Hirschsprung disease, a condition affecting the large intestine, is typically diagnosed through surgery. For this reason, it’s important for pediatric healthcare professionals to understand the various surgical procedures used. These procedures can significantly impact the care and recovery of patients.
Before the surgery, doctors often suggest a procedure called rectal irrigation. This procedure helps to clear out the bowel and reduces the size of the colon, which may help to prevent a severe complication known as enterocolitis, an inflammation of the small and large intestines.
The type of surgery needed will depend on each patient’s individual condition. For example, patients who have a shorter affected segment of colon and do not have other health conditions, might undergo a one-step operation called a pull-through procedure. This operation involves removing the diseased part of the colon and then “pulling” the healthy section down and connecting it to the anus.
If the patient’s colon is overstretched (dilated) or they’re experiencing inflammation (enterocolitis), a two-stage process is often preferred. The first step is a temporary colostomy, which is an opening made in the abdomen to allow waste to exit the body into a bag.
The final pull-through procedure, which basically puts everything back ‘inside’, can be performed approximately four to six months after the colostomy. There are multiple types of pull-through procedures available. The traditional Swenson’s method involves removing the rectum and pulling the healthy part of the colon through and connecting it to the anus. More modern methods, like Duhamel’s and Soave’s, have the added benefit of preserving key nerve networks around the rectum and bladder. Following a Soave’s procedure, it’s extremely important that the patient has frequent sessions to gently stretch the new connection, which can be done at home. All these procedures generally have good outcomes, with minimum complications.
An alternative approach is a single-stage Soave’s procedure performed early on in newborns. This method can potentially avoid the need for a procedure that creates an opening in the abdomen (colostomy) or an incision across the belly. However, the complication rates are quite similar to the more invasive procedures.
What else can Hirschsprung Disease be?
Hirschprung disease, also known as an intestinal dysganglionosis, is a medical condition that needs to be distinguished from other similar conditions. This includes intestinal neuronal dysplasia (IND) and isolated hypoganglionosis (IH). The way to confirm the diagnosis of IND involves looking at certain factors that were defined in 1992. Two of these widely accepted factors include the presence of (1) an overly enlarged sub-layer of mucous in the intestines, and (2) increased activity of a specific enzyme, acetylcholine esterase (AChE), in the submucous layer. Further indications to confirm IND include misplaced nerve cells, abnormal AChE activity in other intestinal layers, and abnormalities in the round muscle layer.
Furthermore, it’s important to differentiate Hirschprung disease from other related conditions that share similar symptoms. These include:
- Intestinal ganglioneuromatosis
- Isolated hypoganglionosis
- Immature ganglia
- Absence of the argyrophil plexus
- Internal anal sphincter achalasia (ISA)
- Megacystis-microcolon intestinal hypoperistalsis syndrome (MMIHS)
ISA can be identified through a specific pathology finding related to the absence of rectosphincteric reflex, while the most common type of IND could be diagnosed based on an increase in the growth of nerve cells (hyperganglionosis) with misplaced (ectopic) nerve cells, and enhanced AChE activity. Certain staining techniques on a biopsy of the rectal tissue could be useful for diagnosing the remaining conditions.
For example, intestinal ganglioneuromatosis, mainly present in the colorectal area, is characterized by an exceptional growth of the sub-layer of intestine mucous and associated nerve trunks, along with scattered mature neurons, and an increase in AChE activity. Isolated hypoganglionosis, a rare diagnosis, might be suggested based on specialized staining techniques. Immature ganglia, which is age-dependent and presents with chronic constipation, might be identified through specific tests and staining techniques.
MMIHS, an uncommon syndrome causing severe obstruction symptoms in newborns, needs further research to establish the exact causes. It’s believed to be linked with genetic mutations, particularly related to the receptor of acetylcholine, a neurotransmitter in the human body.
What to expect with Hirschsprung Disease
The quality of life for people living with Hirschsprung’s disease (HD) often depends on how well they can control their bowel movements. However, there’s still a lack of studies exploring life quality in people who’ve had HD for a long time. In a rare, in-depth survey from France, nearly 3000 adults living with HD filled out a special questionnaire.
This questionnaire was initially designed by a Dutch team in 2001. Their questionnaire explores HD, as well as a range of different anorectal malformations, which are problems with the structure of the anus or rectum. The French study adjusted this questionnaire to better suit their research.
Possible Complications When Diagnosed with Hirschsprung Disease
Hirschsprung disease may lead to several complications, with Hirschsprung-associated enterocolitis or HAEC being one of the common but serious ones. HAEC is an inflammatory condition of the bowel. For a correct HAEC diagnosis, multiple symptoms and signs must be considered, which could sometimes lead to over or under treatment. The exact cause of HAEC is still not entirely understood, but some theories include imbalances in the gut’s bacterial population, weakened surface of the intestine, altered natural immune responses, and unwanted movement of bacteria.
With HAEC, the severity of symptoms can vary, so different grading systems have been created to categorize the different gastrointestinal and overall health signs. These include the Delphi method and a grading system from a research trial focused on three main symptoms, namely diarrhea, bloated stomach, and systemic signs.
Treatment for people with HAEC depends on the severity of their symptoms. For mild HAEC, a regimen of medication, fluids, and electrolytes can be administered at home. However, severe HAEC cases require hospitalization and treatment involving intravenous fluids and broad-spectrum antibiotics. For patients with a bloated stomach, doctors may consider rectal irrigation to reduce bacteria. If standard medical treatments do not work for children with severe HAEC, a surgical procedure called proximal colostomy may be considered.
Apart from HAEC, people with Hirschsprung disease may also face other less common complications after surgery. These can include bleeding, wound infections, painful sores around the anus and abnormalities at the surgical connection site. Others may experience abnormal bowel movements, such as constipation due to high anal resting pressure and weak rectal muscle movements. Additionally, fecal incontinence, or a lack of bowel control, could result from inadequate surgical technique.
Examples of Hirschsprung Disease Complications:
- Hirschsprung-associated enterocolitis (HAEC)
- Abnormal bowel movements (constipation and fecal incontinence)
- Bleeding and wound infections
- Abnormalities at the surgical connection site
- Abnormal anal resting pressure and weak rectal muscle movements
- Painful sores around the anus
Preventing Hirschsprung Disease
While the most serious problems related to Hirschsprung disease may not appear until adulthood, many patients who had surgery for the condition during infancy may experience changes in their bowel habits during their school years. This potential issue can have a substantial psychological impact, disrupt their quality of life, and cause stress for parents, including requiring them to take time off from work. For these reasons, using a team of healthcare professionals to teach the child how to properly use the toilet is crucial. This training involves a few key steps, such as learning the correct ways to have a bowel movement and proper toilet habits.
Parents should be alert to any symptoms that could hint at Hirschsprung disease. These signs include a delay, longer than 48 hours, in the time it takes for a newborn to pass their first stool (meconium). Other, less specific symptoms such as constipation, bloating, acid reflux, nausea, vomiting, and diarrhea should also be cause for concern.
