Rizwan Hamid, M.D., Ph.D., examines baby Joseph Stuewe as his father Daniel holds him during a checkup in the genetics clinic at the Monroe Carell Jr. Children's Hospital at Vanderbilt.
photo by Dana Johnson
Newborn screening helps spot disorders early on
One-month-old Joseph Stuewe is growing well. That's great news, but when his mother expresses concern about how often he eats and how hungry he seems to her doctor, he is careful not to brush her concerns aside. Joseph has a rare metabolic disorder called very long-chain acyl-CoA dehydrogenase deficiency (VLCAD). He was born without a crucial enzyme that breaks down certain fatty acids in the body. Babies with VLCAD can die suddenly — and until recently — without explanation. Now, for the first time, deaths and serious side effects of VLCAD and other disorders have become preventable.
“Had he been born 13 or 14 months earlier, he might have had serious problems,” said Rizwan Hamid, M.D., assistant professor of Pediatrics. “The first event is often critical. They die from sudden infant death syndrome (SIDS), or present to the emergency room either having stopped breathing, or they have lungs filled with fluid.”
Whether any of that might have happened to Joseph will never be known because his disorder was discovered with the aid of newly expanded newborn screening so that steps could be taken quickly to avoid the damage associated with VLCAD. At the beginning of 2004, the state of Tennessee purchased lab equipment capable of taking a small sample of a newborn's blood and checking it for key signs of up to 60 disorders. By year's end all 60 tests had been implemented for all newborn babies in Tennessee. That kind of broad screening is only offered in about 16 states right now.
Joseph's father, Daniel, held his son and played with him recently as his wife, Lindsey talked with Hamid and a genetic counselor at the genetics clinic at the Monroe Carell Jr. Children's Hospital at Vanderbilt. Joseph, a robust 8-pounder at birth, appeared perfect in every way and went home on schedule, but then came a phone call.
“They said the newborn screening had showed there might be a problem, but they said it was so rare and that the test could have false positives, but they wanted to re-test him to be sure,” said Lindsey. “We weren't concerned at all until they called three days later and asked us to come in again — that day.”
It's not surprising Lindsey and Daniel had never heard of VLCAD. It only occurs in one in 40,000 births, and it's only been widely described and studied for about three years.
As long as VLCAD babies have enough sugar in their bodies from regular meals, there's no problem, but when a normal infant fasts for a period of time, the body resorts to breaking down fats for energy.
If Joseph's body ran out of sugar, breakdown of long-chain fatty acids would be incomplete and levels would quickly rise in the baby's body. Long-chain fatty acids can cause heart muscle to get floppy, leading to a dangerously enlarged and weakened heart, and can cause heart rhythm problems and damage both the liver and kidneys.
“The trouble is, we know there is a spectrum of severity, but we don't yet know which babies have more severe cases. That is part of what Dr. Strauss is investigating,” Hamid said.
Arnold W. Strauss, M.D., medical director for VCH and professor of Molecular Physiology and Biophysics, is a leading international expert in VLCAD and related fatty acid oxidation disorders. He says expanded newborn screening is a major development in prevention of childhood illness for babies like Joseph.
“Newborn screening assures that all patients at risk for VLCAD and other related disorders are picked up early enough for preventive treatment,” Strauss said. “It's not that often that you find disorders that have simple, inexpensive prevention as these disorders do.”
Strauss has taken a sample of Joseph Stuewe's blood to sequence the genes and find the mutations that cause his VLCAD. He says he will be able to compare it with a bank of hundreds of samples from around the world with a goal of correlating the type of defect with the outcome of patients.
“We know from previous families that careful supplementation and regularly scheduled feeding usually helps, but we need to know more by comparing cases. That's why we're doing the research in the genetics lab,” Strauss said.
Lindsey had questions for doctor Hamid, but mostly about Joseph’s new formula. Could it be the formulas making him gassy? “Yes” is the answer. And that could be part of why he wakes up crying, but one month is a typical age for babies to develop colic.
“Typical” is what the Stuewes are hoping most of Joseph's problems will be from here on out. They have already had good news about their son's condition.
An echocardiogram performed shortly after his diagnosis found his heart to be perfectly normal, with no sign of the enlargement that often occurs with VLCAD babies. Joseph is on a formula designed to be low in long-chain fatty acids. He is also on a supplement thought to help the body make better use of fatty acids; remarkably simple fixes for such a rare and potentially deadly disorder.
The Stuewes will have to be more vigilant than most parents when Joseph gets the normal viral illnesses that tend to keep babies from eating well.
If he ever has a virus that makes him vomit or have diarrhea, or if a stuffy nose or sore throat make him want to stop eating, they must bring Joseph in to the emergency department to test for buildup of fatty acids. The Stuewes say that is a small price to pay, considering what newborn screening appears to have prevented.