Key Takeaways

  • Hirschsprung’s disease is a rare condition that happens when a baby is born without nerve cells in the lower part of their intestines.
  • The condition makes it difficult for babies to pass stool.
  • Without treatment, Hirschsprung's Disease can lead to other serious medical conditions, like Hirschsprung's associated enterocolitis (HAEC)

What is Hirschsprung’s disease?

 Hirschsprung’s disease (abbreviated as HSCR) is a condition in which there are no nerve cells (known as ganglion cells) in the lower part of your child’s intestine. The affected part of their intestine is therefore “aganglionic,” meaning it is missing ganglion cells. The aganglionic area is usually just in the lower end of the bowel but sometimes continues farther up the colon (large intestine). Since these nerve cells are essential for helping the colon to pass stool, newborns with HSCR are often unable to poop.

HSCR occurs in about 1 in 5000 children, more often in boys. In 90% of cases, HSCR is diagnosed in newborns when they fail to pass meconium (a baby’s first stool). The other 10% of patients are diagnosed later in childhood and occasionally in adolescence or adulthood. In these cases, the condition is usually recognized because the child or adolescent has severe constipation. 

What causes Hirschsprung’s disease? 

HSCR is a disease of the enteric nervous system (ENS), the network of nerve cells that are present throughout the gastrointestinal tract (the digestive pathway through your child’s stomach and intestines). The ENS is responsible for controlling digestive functions like absorbing nutrients from food, pushing food and waste along the intestine, and passing stool.

The nerve cells that form the ENS develop from a group of cells called “neural crest cells” before a child is born. These neural crest cells spread while the baby is developing in the womb, from the esophagus to the stomach, small intestine, and large intestine until they populate the entire length of the digestive tract. HSCR occurs when the neural crest cells fail to complete this migration process and leave the end of the intestine aganglionic (lacking nerve cells). The aganglionosis keeps the digestive tract from functioning properly.

What are the symptoms of Hirschsprung’s disease in babies?

The hallmark symptom of Hirschsprung’s disease is a baby’s failure to poop in the first 48 hours of life. Other symptoms of HSCR in newborns include

  • abdominal distension (stomach swelling)
  • vomiting
  • feeding difficulty

What are the Types of Hirschsprung's Disease 

Hirschsprung’s disease types are classified by how much of the intestine is aganglionic:

  • “Short-segment” Hirschsprung’s disease is the most common form of HSCR, occurring in 80% of HSCR patients. This form of the condition affects the rectum and sigmoid colon, the lowest part of the colon (see Figure below).
  • In “long-segment” Hirschsprung’s disease, the aganglionosis extends higher into the colon, affecting a larger area.
  • Total colonic aganglionosis (TCA) is when the entire colon, and often also the last part of the small intestine, is missing ganglion cells. This version of the condition occurs in 5% of cases.
  • Total intestinal aganglionosis, the least common version of the condition, involves the entire small intestine and the entire large intestine. This form is rare, occurring in approximately 1% of HSCR patients.

How is Hirschsprung’s disease diagnosed? 

When a full-term baby fails to pass meconium stool within the first 48 hours of life, doctors will consider the diagnosis of HSCR. However, it is important to know that up to 50% of newborns who do have HSCR succeed at passing stool within 48 hours. Therefore, while failure to pass stool within 48 hours raises concern that a child may have HSCR, the passage of stool does not rule out the disease.

When there is suspicion that a child may have HSCR, the first step is often a contrast enema. In this test, a catheter (a thin, flexible tube) is placed in the baby’s rectum and injected with a dye while an abdominal x-ray is taken so that the doctor can examine the lower intestine. If a child has short-segment HSCR, the doctor will see an unusually narrow rectum and an unusually dilated colon. If the contrast enema suggests the child has HSCR, or if the child’s clinical history and physical exam are highly suspicious for it, then a biopsy (examination of cells and tissue) is taken from the rectum to be sure of the diagnosis.

A suction rectal biopsy can be performed without anesthesia. It causes minimal discomfort and there is no need for stitches or pain medicine after the procedure. The biopsy is evaluated by a pathologist who looks carefully under a microscope to check whether ganglion cells are present. The pathologist also looks for the presence of thickened nerve fibers, which are also associated with HSCR. Another test that doctors sometimes recommend for patients suspected of having HSCR is called anorectal manometry (ARM). In this procedure, the doctor will expand the rectum by inflating a balloon, which causes the internal anal sphincter to relax in healthy patients. This effect is called the “recto-anal inhibitory reflex” (RAIR). But in patients with HSCR, the sphincter does not relax and the RAIR is absent. Children who do not have a RAIR are diagnosed with HSCR.

How is Hirschsprung’s disease treated?

Surgical removal of the aganglionic bowel is the only treatment for HSCR. Early diagnosis and prompt initiation of medical therapy are important to keep your child healthy and prevent complications.

Once the diagnosis of HSCR is confirmed, doctors will begin your child’s treatment with anal dilations and/or rectal irrigations.

  • Anal dilations are performed once or twice a day to decompress the child’s colon. If the dilations don’t successfully empty the colon, the doctor will start rectal irrigations.
  • Rectal irrigations are performed using a catheter once or twice a day to inject saline (a saltwater solution) into the rectum until the fluid that comes out is clear.
  • If anal dilations or rectal irrigations are effective at decompressing (emptying) the colon, the doctor will teach parents and guardians how to do them at home with their child.

After your child has undergone anal dilations and rectal irrigation, a surgeon will perform pull-through surgery to fix the affected part of the bowel. In this surgery, the aganglionic part of your child’s intestine is removed and the healthy section of their intestine (with normal nerve cells) is attached to the anal canal.

Infants with HSCR generally have surgery within the first six months of age. In children with short-segment HSCR, the surgeon determines the optimal timing for pull-through surgery. Children with long-segment HSCR may need an ostomy bag before the pull-through procedure if the irrigations are unsuccessful in emptying the colon. These patients undergo surgery to create an ostomy (an opening in the small or large intestine) so that their stool can empty into a bag instead of building up. Pull-through surgery is done in children with long-segment HSCR when they are older, usually at least 10-12 months of age. 

After the operation, doctors will help with pain control, monitoring for stool output, and resumption of feeding once the child’s bowel function returns. Starting 1-2 weeks after the procedure, the surgeon may ask parents or guardians to dilate the anus every day to keep it from scarring. Caring for the skin around the anus is also important since skin breakdown from liquid, high-frequency stool can be a major problem for children and their parents. Barrier creams should be applied immediately after surgery to help prevent severe diaper rash.

What are possible complications of surgery for Hirschsprung’s disease?

Most children do very well after their pull-through surgery. Some, however, develop problems with bowel function, including obstructive symptoms, fecal incontinence, and an infection called Hirschsprung's associated enterocolitis (HAEC).

Obstructive symptoms occur when a child has difficulty evacuating stool. There are five possible causes:

  • Mechanical obstruction (when the intestine is blocked)
  • Internal anal sphincter dysfunction (when the anal sphincter muscle does not relax properly to release stool)
  • Transition zone pull-through (when not enough intestine was removed at the first operation)
  • Colonic dysmotility (when the colon doesn’t work properly)
  • Functional constipation (when the child avoids stooling).

Evaluation of a child with obstructive symptoms includes a physical exam (including rectal exam), contrast enema, and rectal biopsy. Depending on the problem identified, treatment may include anal dilation, redo surgery, botox injection, bowel management, or behavioral therapy.

Fecal incontinence (accidental stool leakage) is relatively common in patients with HSCR. Some cases of soiling may be due to “pseudo-incontinence,” which is caused by overflow of stool in a child who is severely constipated and can be treated with bowel management. Soiling can also be caused by an overly active colon or by surgical injury to the anal sphincters or pelvic nerves. Treatment for these problems includes use of anti-motility agents, amitriptyline to reduce colonic activity, a constipating diet, or antegrade enemas.

Hirschsprung-associated enterocolitis (HAEC) is the most serious complication of HSCR. It can appear as an early symptom of HSCR and lead to the diagnosis, but it can also happen after the diagnosis of HSCR has already been made, and even after the child has already had pull-through surgery. Symptoms of HAEC include

  • explosive diarrhea
  • abdominal distension
  • lethargy
  • fever

The incidence (rate of occurrence) of HAEC is hard to determine, largely because there is no stardardized definition of the condition. It occurs in up to 60% of patients before pull-through surgery and up to 42% after surgery. Children with Down syndrome, long-segment aganglionosis, and pre-operative HAEC are at a higher risk of developing HAEC after surgery.

Children with HAEC must begin treatment promptly so that they do not get sicker. Doctors, nurses, parents, and guardians need to be aware of the symptoms of HAEC so that delays in treatment are avoided. If the HAEC is mild, treatment includes oral metronidazole (Flagyl) and rectal irrigations. More severe cases require admission to the hospital for rectal irrigations, IV antibiotics, and IV fluids.

How is Hirschsprung’s disease inherited?

HSCR has a complicated inheritance pattern. About 11 genes have been found to be associated with the disease. Most important among these is the RET gene, which codes for a protein that is expressed on the neural crest cells that give rise to the ENS during fetal development. Many patients with HSCR have a mutation in the RET gene, but other genetic mutations have also been identified.

Most cases of HSCR are sporadic, meaning that they occur randomly in families with no history of the disease. About 20% of cases are familial and these cases are more often associated with long-segment disease. Several genetic syndromes are also associated with HSCR. The most common among these is Down syndrome (Trisomy 21), which affects 10% of all children with HSCR. 

Future developments in treating Hirschsprung’s disease

One area of active research is the development of stem cell therapy for HSCR. The idea is that neuronal stem cells can be isolated from the intestine and grown in a dish. These cells could then be transplanted into the aganglionic intestine to replace the missing nerves. Several labs around the world are working on this as a possible new therapy for Hirschsprung disease with the goal of avoiding the need for surgery and improving long-term outcomes for patients. However, scientists have not yet shown that the transplanted cells can improve intestinal function. This research is still only being done on animals, but hopefully studies in humans will start in the near future.

Other areas of research aim to prevent or treat HAEC. As a first step, researchers are trying to understand what causes HAEC in the first place. Disease-causing bacteria present in the intestine of children with HSCR have been identified, and some scientists hope that probiotics might reduce the risk of HAEC by restoring normal, healthy gut bacteria. However, there is no convincing evidence that shows a definite relationship between any specific group of bacteria and the development of HAEC. Other abnormalities in the intestines of HSCR patients may also contribute to the development of HAEC, and these are being actively studied.

Finally, much research is being done on the quality of life of HSCR patients and how to improve it. One study suggests that the involvement of mental health professionals in the management of children with HSCR is very important to improve their social and emotional well-being. Another article emphasizes the need to address care transitions as children with Hirschsprung’s enter adulthood. Not planning for this important transition to adult medical care can lead to lapses in care that can negatively impact a patient’s quality of life. Smooth transitions of care from childhood into adulthood are essential to ensure that these patients’ medical needs are adequately met by the appropriate care providers.

To learn more about Hirschsprung’s disease, or to learn how you can help support the research being done to cure the disease, contact Dr. Allan Goldstein, Chief of Pediatric Surgery at MassGeneral Hospital for Children, at amgoldstein@partners.org.