Oct. 18, 2000 (Washington) -- Almost 40 years after the U.S. began screening all newborns for phenylketonuria (PKU), a panel of experts has issued the nation's first consensus standards for how to diagnose and treat this metabolic disorder, which, if left untreated, can lead to profound mental retardation.
PKU is a rare, inherited disorder associated with a deficiency of a liver enzyme. This deficiency leads to the accumulation of an amino acid called phenylalanine in the blood and tissues. That can result in brain damage early in childhood that continues into adulthood, usually resulting in mental retardation. Treatment requires avoiding foods with this amino acid, which is a building block of proteins.
The standards released Wednesday were developed by an independent panel of experts assigned by the National Institutes of Health to resolve questions about the diagnosis and treatment of this disorder. Although the research on PKU continues to broaden, its treatment and diagnosis now varies from state to state and physician to physician, due mostly to the lack of clear-cut policies.
For instance, while some states offer follow-up services such as counseling to the families of those with the disorder, others do not offer the social services families may need to address the school, family, and behavioral difficulties that can accompany PKU. And while some doctors recommend ending treatment after childhood, others say it should continue throughout the patient's lifetime.
Among the panel's recommendations were that treatment be lifelong and that pediatricians caring for children with PKU adopt a multidisciplinary approach that includes encouraging family counseling. The panel also recommended that states develop policies to help these families get the medical services they need and to ensure that appropriate screening, treatment, and data collection are taking place.
Despite the panel's efforts to include caveats, such as the need for further research into the causes and mechanisms of PKU, not everyone supports its recommendations.
"You have got to remember that there is such a thing as junk science," says Samuel Bessman, MD, chair of pharmacology and professor of pediatrics at the University of Southern California School of Medicine.
According to Bessman, the panel's recommendations largely ignore the fact that some patients with PKU never develop mental retardation. They also ignore the fact that treatment of PKU can itself have harmful effects, and that the most commonly used diagnostic test for PKU is not 100% accurate, he says.
"My fear is that they are making suggestions based on numbers that are not wholly accurate," he tells WebMD.
The current treatment for PKU involves putting patients on a diet that excludes all high-protein foods, such as milk, eggs, and nuts. The reason is that all protein contains phenylalanine. When a strict diet is begun early and phenylalaline levels are controlled, experts believe that children with PKU can develop normally.
But the treatment itself can be dangerous and difficult to maintain since it also requires the diligent use of supplements, Bessman says. And due to the limited amount of research conducted on PKU, there's no evidence to demonstrate that everyone needs treatment or that mandatory screening is necessary, he tells WebMD.
PKU is thought to occur in about one in every 15,000 children, he says. That means the average hospital will see one case every four years, and the average pediatrician will see about one case during his or her lifetime, he says.
Still, the panel has full confidence in its recommendations, says Rodney Howell, MD, the panel chair and the chair of pediatrics at the University of Miami School of Medicine.
"The bottom line is that the average IQ of someone left untreated is 19," he tells WebMD. In essence, that means about 98% of people with PKU would require institutionalization if they were not treated, he says. Patients who are put on the diet generally go on to live normal lives, doing everything from attending college to raising families, he says.
"There is no question that the treatment has been remarkably effective," Howell says.
As for mandatory screening, "it's the best buy in the world," Howell says. At a cost of about $1.50 per test, it provides peace of mind, he says. It also ensures that people with PKU are diagnosed within the first few days of their lives, so precautions can be taken at a time when the damage to their brains could otherwise be substantial.
But further research is needed concerning the roughly 2% of patients with PKU who do not develop mental retardation despite not being treated, Howell concedes. States also should be encouraged to keep better data to aid in the development and testing of new treatments, and health officials should be encouraged to treat the diet as a medical necessity so that families can defray the costs, he says.
New treatment options are being studied, and experts believe there may someday be a genetic treatment to replace the diet. In the meantime, despite some doctors' reluctance to sign on, the standards are likely to be adopted by many pediatricians and states, Howell says.
Physicians are not bound by the standards, but studies done before and after other consensus conferences have shown that they can affect the diagnosis, treatment, and management of diseases and disorders, he says. Such standards also can influence insurance reimbursement policies, thus indirectly affecting doctors' behavior.
"We hope very much that it will have an impact," says William Rizzo, MD, a member of the panel and a professor of pediatrics and human genetics at the Medical College of Virginia in Richmond.