Unusual prenatal MRI detects rare, oft-missed genetic disease
The disorder, congenital chloride diarrhea, can cause severe dehydration and serious metabolic disturbances in newborns if not treated quickly.
“This is a disease where early diagnosis is the key to a good outcome,” said Richard Barth, MD, the physician who recognized the unusual case. Congenital chloride diarrhea is so rare, with only about 250 total cases reported worldwide, that infants with the disease are often erroneously treated for other diarrhea-causing ailments. “If the patient’s fortunate, you could stumble onto this diagnosis,” said Barth, the chief radiologist at Packard Children’s and a professor of pediatric radiology at the School of Medicine. The case was the first instance of CCD Barth had ever seen.
It is one of only four known cases of CCD diagnosis ever made via prenatal MRI. A scientific report on the four cases, including Barth’s case and three from France, was published online Dec. 9 in the journal Ultrasound in Obstetrics & Gynecology. The report is a collaboration between Barth and a team of French scientists in Marseilles.
Barth made his diagnosis in February 2009 when an expectant mom was referred to him for follow-up of an abnormal prenatal ultrasound. The ultrasound showed classic signs of bowel obstruction, a fairly common fetal problem. To get more information about the fetus, Barth ordered an MRI scan, which gave him a surprise that could not have been detected by ultrasound: Instead of showing the fetal colon filled with solid waste, as in a bowel obstruction, it was filled with fluid. This important clue, found thanks to the Packard team’s expertise in fetal MRI, pointed Barth toward the obscure diagnosis of CCD. “The baby’s dad said, ‘You’re coming up with a real zebra here,’” Barth recalled.
But that “zebra” saved the new baby a lot of trouble when she was born at Packard a few weeks later.
Barth collaborated with obstetrics and neonatology teams in the hospital’s Johnson Center for Pregnancy and Newborn Services to ensure the infant’s fluid and electrolyte levels would be monitored starting at birth. This was needed because the gene mutation that causes CCD damages a salt-transporting protein in the intestine. The abnormality stops the body from absorbing essential electrolytes, causing patients to have large amounts of watery, high-salt diarrhea.
“These babies can go into shock and die because of the tremendous electrolyte imbalance at birth,” said Maurice Druzin, MD, professor and service chief of obstetrics and gynecology at Packard Children’s.
Without the prenatal diagnosis, it could easily have taken physicians a few days to figure out what was going on, Druzin said. “The baby could have been in serious trouble by that time,” he added.
Untreated patients who survive early life may suffer permanent kidney damage, feeding problems, severe malnutrition and delays in growth and motor development.
“In this case, the neonatology team was not just monitoring the baby’s electrolytes, but also taking special precautions in terms of feeding,” said neonatologist Susan Hintz, MD, associate professor and medical director of the Center for Comprehensive Fetal Health & Maternal and Family Care at Packard Children’s. “We took these steps due to the strong possibility that this was CCD.”
For infants whose CCD is detected early, treatment is straightforward: intravenous fluid and salt replacement can compensate for their ongoing diarrhea. As they get older, patients may take extra liquids and salts by mouth, or they can opt for newer treatments.
For instance, the little girl Barth diagnosed is now taking an oral medication that modifies her body’s salt uptake and reduces diarrhea. Although these treatments do not cure the disease, prompt diagnosis and treatment allow patients to lead fairly normal, healthy lives.
“Dr. Barth’s experience with difficult cases and the depth of his familiarity with the fetal imaging scientific literature really helped our entire team provide the best possible care for this mother and baby,” Hintz said.
The patient, whose rare diagnosis was further confirmed by genetic testing in December, is now a thriving 1-year-old. Her parents report that she’s starting to walk and has three teeth.
“We are grateful to Dr. Barth,” said the patient’s mother. “He went out on a limb by diagnosing our baby with an extremely rare disorder and then stood behind his diagnosis, which provided the team with the right direction of treatment. His mood was mixed with both excitement for the technological finding and clear compassion for our circumstances.”
Looking back at this extraordinary case, Barth saluted the comprehensive care Packard Children’s offered the newborn and her family.
“When there’s a fetal anomaly like this, families face an emotional tsunami,” Barth said. “But our imaging teams have experience taking on some of the toughest cases in the world, and our collaboration with other hospital subspecialties is really what multidisciplinary care is all about.
“This reassures families that good outcomes are possible even in the rarest of cases,” he said.