WASHINGTON - Doctors were stumped. Tests for meningitis, cancer, a list of other diseases all were negative -- yet just days after a sudden high fever sent 8-week-old Anthony James Mingione to the hospital, he died. An autopsy uncovered the lethal secret: Anthony was born without a working immune system. A rare genetic disorder known as the "bubble boy disease" rendered him vulnerable to the most minor of germs.
Now Wisconsin is about to begin the nation's first experiment at testing newborns for this killer, officially named SCID, in hopes of giving babies like Anthony a chance at lifesaving treatment -- even as scientists ask how many infant deaths attributed to infections really might be due to the immune destroyer.
"These people look like the Gerber baby until they get sick," says Dr. Rebecca Buckley, a SCID specialist at Duke University and longtime advocate for newborn screening.
"I am more concerned than ever that a lot of these babies never make it to the pediatrician, much less an immunologist."
Between 40 and 100 U.S. babies are estimated to be diagnosed each year with SCID, or "severe combined immunodeficiency disease." The best-known victim was Houston's famous "bubble boy" who lived in a germ-proof enclosure until his death at age 12 in 1984.
But no one knows how often SCID is missed. In a few dozen more cases? Another 100?
"We think there's a lot more out there and that the infants just die," says Dr. Jack Routes, a pediatrician at Children's Hospital of Wisconsin. He is heading the newborn-screening experiment, with funding from a parents' advocacy group, the Jeffrey Modell Foundation, that may help answer that question.
Catching the disease before a baby gets sick means a far better chance that treatment is successful, explains Dr. Jennifer Puck of the University of California, San Francisco.
Puck developed the first screening test that promises early diagnosis. This winter, Wisconsin's state laboratory begins the first phase of its pilot project, practicing with Puck's test on anonymous newborn blood samples. If no problems crop up, later this year Routes and colleagues will begin a study that attempts to screen all Wisconsin newborns for SCID -- to see how accurate it really is, and track what happens to those diagnosed.
"I know this will change the course of SCID," says Anthony's mother, Tara Mingione of Long Island, N.Y., who has pushed for screening since his death two years ago. "Anthony had absolutely no chance to live unless he was tested at birth."
Today, all U.S. newborns are tested for a variety of rare but devastating genetic diseases -- using a single spot of blood from the baby's heel a day after birth -- to catch the few thousand who need fast treatment to avoid serious problems.
Not yet on that list: SCID and other "primary immunodeficiency" diseases, meaning children are born with faulty immune-system genes. There are different SCID subtypes, but the end result is that babies can't produce important disease-fighting cells called T cells.
Without treatment, they usually die before their first birthday. Bone marrow transplants can provide them with stem cells that take root and begin producing T cells after all, curing some children and greatly extending the lives of others.
But Duke's Buckley calls age key: She reports 95 percent survival in SCID babies transplanted before they're 3 months old -- almost always those born to women who know SCID has struck a relative, and thus seek at-birth testing. After that age, survival plummets because the babies are so sick going into surgery.
Moreover, total costs for transplanting a baby shortly after birth are about $100,000, Buckley says, compared with bills that can reach $1 million after they get sick.
When doctors suspect a baby has SCID, they can check a vial of his or her blood to see if T cells are present. But routine screening -- checking those dried blood spots -- requires a whole different approach.
Puck had to create a kind of DNA test to detect bits of genetic material that signal T cells' maturation, and thus should be visible only in healthy babies.
It's not perfect, cautions Robert Vogt, a research chemist at the Centers for Disease Control and Prevention. But it seems accurate enough to study in thousands of babies, scientists concluded at a November meeting sponsored by CDC and Modell Foundation. Vogt says California, New York and Missouri are among a handful of other states considering pilot screening projects.
Also, CDC is funding California health officials to use the new test to check stored blood samples from nearly 2,000 babies who died before 18 months of age -- probing whether SCID gets missed.
Mingione is convinced it does, because she almost turned down the autopsy that finally diagnosed Anthony. To avoid chancing another tragedy, last spring she adopted a healthy baby boy.
