Before 1995 no U.S. state had screened babies for more than eight disorders. A decade later some states were screening for anywhere from seven to 52. States lacked clear consensus on which disorders warranted man- datory screening, says Michael Watson, executive director of the American College of Medical Genetics and Genomics. To remedy the situation, the Health Resources and Services Administration commissioned Watson to review the scientific literature on 84 disorders and to determine which of the screens clearly benefited newborns.
In a report made in 2005 Watson recommended that all states screen for 29 disorders that doctors could clearly predict and treat. He further advised against screening for Krabbe and other diseases because there was not enough evidence that early intervention did more good than harm. Most states currently screen for all 29 recommended disorders, but some, like New York, also test for Krabbe or other conditions outside the uniform panel—including Pompe (a muscle-weakening disease) and Fabry (a metabolic disease causing severe pain). The outcomes of New York's decision to screen for Krabbe underscore why some doctors believe that enthusiasm for screening has gone too far.
Since its inception in 2006 New York's program has tested one million babies and identified more than 200 infants with unusually low levels of some enzymes, indicating risk for Krabbe. Lab technicians verify these results with both enzyme and genetic tests. What investigators have found has been surprising.
Of the 228 infants who tested positive for Krabbe, 24 were found to have genetic markers associated with the disease. So far, however, only four of those children have developed Krabbe symptoms, whereas the other 20 continue to appear healthy. In the vast majority of cases, symptoms of Krabbe appear in early infancy and quickly worsen. A few reports in patient registries describe infants who developed symptoms—albeit mild ones—later in life. The 20 New York infants who screened positive for genetic markers of Krabbe but have not yet shown symptoms may have this late-onset form of Krabbe.
But researchers do not understand late-onset Krabbe well enough to know when, if ever, any of these children will develop symptoms. Only when clinicians detect nerve damage in a battery of invasive neurological exams, including brain imaging and a spinal tap, can they be sure that a child has Krabbe. And only then are they certain that treatment justifies its inherent risks. Studies have shown that early stem cell transplants sometimes stop the disease from progressing, although around 30 percent of children do not survive the procedure and all who do still have trouble speaking and moving their limbs.
Many of the 20 children whose tests suggest late-onset Krabbe but who are not yet sick continue to get neurological exams about every four to six months. Some researchers call these children “patients in waiting.” As Jennifer Kwon, a neurologist at University of Rochester Medical Center, puts it, “There's this whole group of children nobody expected to find.” The problem, Kwon says, is that parents of patients in waiting do not know what to do with the information they receive from doctors or even what to expect. Parents begin to worry excessively, become overprotective, pursue risky tests and procedures, and avoid routine ones. “It's a huge burden for parents to carry around this knowledge that many of them didn't ask for,” agrees Melissa Wasserstein, a pediatrician at Mount Sinai Hospital. “Every time their child so much as trips and falls, they're thinking, ‘Oh, my God, does this mean the start?’”
Patricia K. Duffner, who directs the research arm of Hunter's Hope at the University of Buffalo, counters that many parents prefer to know about their child's risk because, if symptoms appear, they will not lose time searching for a diagnosis.