Category Archives: Total Aganglionosis
(Image courtesy of http://en.wikipedia.org/wiki/Ondine’s_curse)
Have you ever heard of the legend “Ondine’s Curse?” Would you believe it could happen in real life?
Myth says that Ondine, a water nymph had a mortal lover. He swore to her that “his every waking breath would be a testimony of [his] love.” Unfortunately, one day, Ondine found out that her lover was unfaithful, and thus cursed him: “should he fall asleep, he would forget to breathe.” Eventually, he fell asleep from sheer exhaustion, and his breathing stopped.
Seven years ago, when I was still a neonatology fellow, we received a call from south of Manila, referring a patient for transfer and further care. The baby was male, born full term from an apparently unremarkable prenatal background. I was the one on deck to fetch baby from the referring to the hospital, and it was an exhaustive three hours trip (one way, as SLEx was under construction that time).
The baby had distended abdomen. He also had several episodes of cessation of breathing (apnea) (which is unusual for term babies, unless there is a problem elsewhere, particularly the brain or lungs). Initially, infection was suspected but despite adequate antibiotic coverage, it did not resolve, hence the referral.
Once baby reached my training hospital, one thing we focused on was his enlarging abdominal girth. It seemed that baby has a form of intestinal obstruction — if baby feeds, the milk is retained thus he will vomit; on the other end, there was no passage of meconium – baby’s first stools. Work-up revealed that he seemed to have Hirschsprung’s disease (segment of the intestine does not have innervation/nervous network – thus the obstruction is not anatomic but rather functional). Usually, babies with Hirschsprung’s disease will only have a segmental involvement of the large intestine (colon); few though may entire colonic affectation (termed microcolon). Unfortunately for our patient, he indeed had microcolon.
Fig A. Microcolon on barium enema
(Image courtesy of http://www.radrounds.com/photo/microcolon-1)
(Image courtesy of p://www.sonoworld.com/fetus/page.aspx?id=226)
Fig B. Normal Barium Enema (Note the contrast on the diameter of the large intestines between Fig A and Fig B).
Microcolon is a form of aganglionosis (meaning, the entire large intestine is devoid of nerve ganglia that’s responsible in controlling its movement/peristalsis, so that food can be moved from the stomach to the anus. Without such ganglia, the intestinal segment becomes obstructed, food remains at the stomach or other parts of the intestine, cause distention and retrograde efflux/vomiting. This is what our patient had.
He was referred to a pediatric surgeon, but operation to take out affected intestinal segment was no longer considered beneficial to the patient. If the entire large intestine is removed, it will eventually lead to malabsorption syndrome, possibly short bowel syndrome also, conditions detrimental to the baby. So only a segment was removed, and a biopsy of the proximal segment of the colon was obtained confirming absence of ganglia. If ganglion cells were absent in the proximal as well as the distal segments, then most likely the entire colon was devoid of ganglia as well.
After baby’s operation, we wanted to remove the respirator that had been assisting his breathing the past days, so he could breath by his own already. We were able to do this after a few days. Then while baby was already spontaneously breathing, meaning without the respirator, we noted that there were episodes of him becoming bluish (cyanotic), and when blood gas was done, he had been retaining carbon dioxide in his blood. At first it was a baffle, but then we noted that these episodes particularly happened when the baby was in his deep sleep. HE WASN’T BREATHING (apnea)! Curious that we were, we all trooped to our textbooks and looked for the definition of congenital central hypoventilation syndrome (THE CURSE OF ONDINE). We worked up baby further to rule out other possible causes why he always had apnea but all were normal.
CCHS is a condition wherein when awake, patients seem normal, they breath normally. But when asleep, they stop breathing, with progressive retention of carbon dioxide (hypercapnea) and low oxygen in the blood (hypoxemia). In normal individuals, when they have hypercapneic episodes, this will stimulate them to breath faster to expel the unwanted carbon dioxide. Unfortunately, patients with CCHS are not stimulated to rebreath, hence this may eventually lead to their death, if not awaken. Therefore, these patients will require ventilatory assistance while asleep, but not when fully awake.
But what is the connection between the baby’s Hirschsprung’s disease (Total Aganglionosis) and this CCHS? Could they be a manifestation of just one disease entity? Or is the baby just unfortunate to have both disease at the same time?
I was so lucky to have a very diligent resident. She was able to find a disorder pertaining to the abnormality of neural crests, or small nerve tissue, that migrate from the central nervous system to peripheral location, including the intestines. It seems that there is abnormal or no migration of this ganglion cells to the intestines, and thus, resulting to Hirschsprung’s disease. But if the absence of ganglion cells involve the entire colonic segment, then that leads to total aganglionosis (a worse variety of Hirschsprung’s disease). Some of these neural crests too eventually end up as chemoreceptors for our breathing. As chemoreceptors, it is their function to detect abnormal concentrations of carbon dioxide and oxygen in our blood. If it detects hypercapnea, then that triggers our brainstem to send signal and increase the work of breathing. In patients with CCHS, there seems to be absence of these chemoreceptors. A worst case scenario, is thus a combination of both aganglionosis, and CCHS in a syndrome called HADDAD SYNDROME. This is what out patient have. At the time my resident was checking if there’s registry for this condition, she saw about 44 patients worldwide so far. That makes our patient possibly 45th. In the Philippines, our case was the first reported one.
My mentor then explained the condition of the baby. He will be needing a pacemaker that will help him regulate breathing while asleep, but the technology is not yet available locally at that time. Alternatively, baby required to be on respirator when asleep, but that would mean intubating baby every now and then. The parents are young and well off, but they knew that this will eventually drain their finances, with no guaranteed positive outcome. They then decided bring baby back to the previous hospital that referred him to us, and discontinued other aggressive treatment measures for the baby. In less than 48 hours, baby expired.