About PKU

Phenylketonuria (PKU) is a rare, inherited, metabolic genetic disorder characterized by the inability of the body to utilize the essential amino acid, phenylalanine. Individuals with PKU accumulate too much phenylalanine, which is one of the amino acids found in protein-containing foods. For unknown reasons, an excess of phenylalanine in an infant's body is harmful to the development of the brain causing mental retardation unless treated during infancy. When a very strict diet is initiated early and well maintained, individuals diagnosed with PKU can expect normal development and a normal lifespan. Treatment consists of lifelong dietary management and counseling, as well as continued blood phenylalanine monitoring.

PKU is caused by mutation in the gene that alters the function of the enzyme phenylalanine hydroxylase (PAH). This enzyme would normally convert phenylalanine to the amino acid tyrosine. In those individuals with PKU, the failure of the conversion results in a buildup of phnenylalanine. Through a mechanism that is not well understood, the excessive amount of phenylalanine is toxic to the central nervous system and causes the severe problems associated with PKU. Damage to the brain causes marked mental retardation by the end of the first year of life. Older children may develop movement disorders: hyperactivity, seizure, speech delays, behavior abnormalities, and delayed mental and motor skills.

In those individuals diagnosed with PKU, each will have varying amounts of enzyme deficiency. Some individuals have enough enzyme activity that the diet can be extensive, while others may have a very strict diet. The healthcare professionals at a PKU treatment program must determine the nature of the diet for an individual diagnosed with PKU.

In "classic" PKU, the enzyme is completely or nearly completely deficient. Without this enzyme, phenylalanine and its' breakdown chemicals from other enzyme routes, accumulate in the blood and body tissues. Molecular analysis of mutant PAH chromosomes identifies over 175 mutations.

PKU is inherited as an autosomal recessive trait. Two people who conceive a child must both be carriers of the gene in order for there to be a chance that the baby will have PKU. When two carriers conceive a child, there is a one in four (25%) chance with each pregnancy that the baby will have PKU. Carriers do not have symptoms of this metabolic genetics disorder.

Incidence and Prevalence

Approximately one of every 10,000 infants born in the United States is diagnosed with PKU. The incidence varies in other parts of the world, as shown below:

There are large variations in the incidence of PKU by ethnic group. The incidence in Whites and Native Americans is higher than the incidence in Blacks, Hispanics and Asians. PKU disorders are equally frequent in males and females.

In 2002, the latest year for which figures are available, the National Center for Health Statistics reported 4,019,280 births in the United States. At the incidence rate of 1:10,000, approximately 400 births were diagnosed with PKU in the United States in 2002. It is estimated that approximately 15-20,000 individuals as infants, adolescents and adults reside in the United States with PKU.

Newborn Screening

PKU is a genetic inborn error of metabolism that is detectable during the first days of life with appropriate blood testing via newborn screening. Universal screening of newborn babies began in the United States almost 40 years ago with the discovery of the cause of PKU and the blood test designed to detect this metabolic genetic disorder. Dr. Robert Guthrie of the University of Buffalo developed the newborn screening test for PKU in 1961. He worked tirelessly to establish newborn screening programs in the United States and many other countries. In 1963, Massachusetts became the first state to mandate screening for a genetic disorder. The Guthrie test for PKU is now mandated by all 50 states and the District of Columbia. Early screening and special diets have allowed these children to grow normally and live full and productive lives.

Treatment

Treatment of those affected with PKU includes a strict diet regimen that is low in, or free in phenylalanine, particularly when the child is growing. The diet eliminates all of the high protein foods, since all protein contains phenylalanine. Such a diet includes fruits and certain vegetables and cereals. A typical diet does not allow the consumption of meat, poultry, fish, milk, eggs, ice cream, cheese, legumes, nuts, or products containing flour.

To prevent mental retardation, treatment must begin in early infancy to ensure normal mental development. Special infant formulas can be used as a protein source that is very low in or do not contain phenylalanine and properly balanced for the remaining amino acids. The diet is supplemented with varieties of low protein foods that are manufactured as an alternative to the formulas. Although the special formulas and medical foods are expensive, a number of states have mandated coverage for these food costs, or in some instances the state health departments provide the special formulas to the families of affected children.

People that have PKU should avoid aspartame, an artificial sweetener (NutraSweet) that contains phenylalanine. In the United States, labels on soft drinks and other foods sweetened with aspartame must carry a warning to people with PKU.
In the early days of treating individuals with PKU, physicians believed that the specialized diets could be discontinued at the early age of 6-10 years. However, it is now clearly recognized that stopping the diet can result in a variety of serious problems. Individuals with PKU that are "off diet" can have behavior problems such as hyperactivity and irritability, drops in IQ, learning disabilities, eczema, and personality disorders. As a result of these problems associated with the discontinuation of the diet, it is believed that the diet should be maintained for life.

It is especially important for women that have PKU and plan to become pregnant to adhere to a strict low phenylalanine diet both before becoming pregnant and throughout pregnancy. Women with PKU that have high blood levels of phenylalanine have a high probability of harming the fetus. Maternal PKU has become a significant concern for risk to a child born to a mother whose blood phenylalanine levels are poorly controlled. A lesser risk of spontaneous abortion, microcephaly, mental retardation, or congenital heart disease has been associated with those mothers having good blood phenylalanine control. Many children born to mothers with PKU have normal growth and development as a result of the mother's early and strict control of blood phenylalanine levels.

The prognosis for those individuals diagnosed with PKU is expected to be good if dietary treatment is initiated immediately after the birth of the child. Typically, if treatment is delayed, brain damage is inevitable. Severe mental retardation occurs if the disorder is untreated.

The treatment of PKU is complex; requiring routine collection of blood samples, maintenance of a highly restrictive diet, recording of food intake, and visits to a PKU treatment program while under strict medical supervision. Barriers to adherence include multiple factors associated with the treatment regimen itself, as well as economic factors, psychosocial issues and health care system issues.

The goal of PKU treatment is to maintain a blood phenylalanine level between 2 and 10 mg/dL. Some phenylalanine is needed for normal growth and body functions. This requires a diet that has some phenylalanine included, but in much lower amounts than normal. Typically, one gram of protein contains approximately 50 mg of phenylalanine.

- Information Provided with Permission from MetGen, Incorporated