NIH Consensus Panel Recommends Comprehensive Approach to Life Long Care for PKU

People with the rare metabolic disorder phenylketonuria need to adhere to the special diet central to their treatment, concluded a Consensus Panel convened by the National Institutes of Health. The conclusion addresses a long-standing difference of opinion about whether people with phenylketonuria could abandon the diet after early childhood.

Phenylketonuria (PKU) is an inherited disorder that, if untreated, causes profound mental retardation as well as other medical problems. The disorder, which affects about one of every 15,000 infants in the United States, usually results from a deficiency of an enzyme known as phenylalanine hydroxylase. This deficiency leads to elevated levels of the amino acid phenylalanine (Phe) in the bloodstream. Screening newborn infants for PKU is standard practice throughout many parts of the world.

"As a result of the screening programs that began nearly 40 years ago, thousands of children with PKU have been identified and treated," said R. Rodney Howell, M.D. Chairman of the Consensus Panel. "Most of these children have grown into healthy adults when they would otherwise have developed mental retardation and other problems associated with PKU."

The current treatment for PKU involves dietary modification and generally excludes all high protein foods, such as meat, milk, eggs, and nuts, since all protein contains phenylalanine. Bread and other wheat products also are excluded. The diet includes special Phe-free foods that supply nutrients that the restrictive food choices lack.

The panel stressed that the dietary control of PKU is only one component of a lifelong treatment program, which should include frequent blood tests, daily dietary logs, and regular, frequent visits to a PKU clinic.

"Although we've made enormous gains, we need to assure that everyone has access to culturally sensitive age-appropriate treatment programs," Dr. Howell added.

The panel issued its statement at the conclusion of a 3-day NIH Consensus Development Conference on Phenylketonuria (PKU): Screening and Management. The conference, held October 16-18, 2000 at the NIH, brought together national and international experts to present the latest research findings on PKU epidemiology and genetics, screening strategies, and treatment regimens.

The panel also recommended beginning treatment for all newborns with the disorder within 7 -10 days after birth to reduce Phe levels as rapidly as possible. In addition, the panel agreed upon target phenylalanine levels for infants and children through 12 years (2-6 mg/dl) and for individuals over age 12 (2-15 mg/dl). Noting the limited data available on the relationship between Phe level and brain function after 12 years of age, and the fact that brain development continues during adolescence, the panel encouraged even lower Phe levels (2-10 mg/dl) during this age period.

Panelists underscored the importance of controlling Phe levels in women of childbearing age with PKU. Non-PKU children exposed to high levels of Phe in the womb are vulnerable to mental retardation, congenital heart disease, and other disorders.

The panel called for uniform policies to remove the individual and the family financial barriers to medical foods, modified low-protein foods, and access to support services required to maintain appropriate Phe levels. Panel members also called for a comprehensive, integrated system to deliver care to people with the disorder, consistency among screening, treatment, and data collection and patient support programs. Currently there is variation regarding newborn screening practice in the United States as well as for criteria defining positive PKU tests.

Panel members also noted that dietary restrictions can be difficult to follow, and dietary nonadherence can result in decline of mental and behavioral performance. For this reason, the panel called for research to examine a wide range of potential new treatments other than dietary therapy. These might include the development of drugs to break down Phe as well as investigating the possibility of gene therapy to replace the defective enzyme in PKU.

The NIH Office of Medical Applications of Research and the National Institute of Child Health and Human Development sponsored the conference. Cosponsors included the National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Nursing Research, and the Maternal and Child Health Bureau of the Health Resources and Services Administration.

The full NIH Consensus Statement on Phenylketonuria (PKU): Screening and Management is available by calling 1-888-NIH-CONSENSUS (1-888-644-2667) or by visiting the NIH Consensus Development Program Web site.

The consensus statement is the report of an independent panel and is not a policy statement of the NIH or the Federal Government. The NIH Consensus Development Program was established in 1977 to resolve in an unbiased manner controversial topics in medicine. To date, NIH has conducted 112 such conferences addressing a wide range of controversial medical issues important to health care providers, patients, and the general public.


An audio report of the conference results will be available after 4 p.m. October 18, 2000 from the NIH Radio News Service by calling 1-800-MED-DIAL (1-800-633-3425).


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