What is PKU?By Virginia E. Schuett, MS, RD, Director, National PKU News
PKU (phenylketonuria), in its “classic” form, is a rare, inherited metabolic disease that results in mental retardation and other neurological problems when treatment is not started within the first few weeks of life. When treatment is begun early and well-maintained, affected children can expect normal development and a normal life span. (Not all elevations of blood phenylalanine require treatment; any child with a level less than 6 mg/dl does not need to be on a special diet and is not risk for mental retardation.) Until recently, the only treatment was a very strict diet that limits the amino acid, phenylalanine. Now, however, there is a drug called Kuvan that can help in some cases.
The Enzyme Deficiency
The disease arises from the absence of a single enzyme called phenylalanine hydroxylase. This enzyme normally converts the essential amino acid, phenylalanine, to another amino acid, tyrosine. Failure of the conversion to take place results in a buildup of phenylalanine. Through a mechanism that is not well understood, the excess phenylalanine is toxic to the central nervous system and causes the severe problems normally associated with PKU. Not every child has the same degree of enzyme deficiency and thus the treatment for each child has to be individualized. The nature of the treatment for an individual child must be determined by an experienced PKU treatment program.
PKU is carried through an "autosomal recessive" gene. This means that two people who conceive a child
must both be "silent 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 (or 25%) chance for each pregnancy that the baby
will have PKU. The incidence of carriers in the general population is approximately one in fifty people,
but the chance that two carriers will mate is only one in 2500. Carrier tests are available only through
PKU treatment programs.
Because of the very positive outcome when children are treated early and well, newborn screening for PKU is carried out in every state in the US and in many other countries. Such screening started in the mid-1960's. Although PKU affects only one out of every approximately 10,000 babies born in the US, there are several hundred babies diagnosed and put on the diet each year. Children with the severe form of PKU once were destined to become mentally retarded and spend their lives in institutions. Children with the disease are now growing up normally. They are attending college and becoming productive adults as doctors, lawyers, teachers and engineers because of early diagnosis and strict treatment.
The diet for PKU was developed in the 1960’s, and until December 2007 when the new drug Kuvan was approved by FDA,
it has been the ONLY treatment shown to be effective.
In the early days of treating PKU, clinicians believed that treatment could be stopped at an early age (6-10 years).
However, it is now known that stopping treatment can result in a variety of serious problems, especially for those with
“classic” PKU, the most serious type. These include drops in IQ, learning disabilities, behavior problems such as
hyperactivity and irritability, neurological problems such as tremors, eczema (a skin disorder) and personality
disorders (including schizophrenia, panic attacks and agoraphobia).
Continuing the diet or returning to the diet for women who have stopped it is especially important for young women with PKU who want to become pregnant. Kuvan is not suitable for women who are pregnant, as it has not been tested for this group of women, so diet treatment is mandatory. Women with PKU who have high levels of phenylalanine in their blood have a very large probability of harming their unborn baby. "Maternal PKU" has become a significant concern as young women who were once taken off the diet are now reaching childbearing ages in ever-increasing numbers. A large collaborative study has shown that returning the woman to diet before conception and keeping blood phenylalanine levels below 6 mg/dl results in the best outcome for the baby. Many children born to mothers with PKU are developing normally because of early and strict treatment.
PKU Treatment Programs
There is at least one specialized PKU treatment program in most US states. In some less-populated states, families may need to travel to another nearby state, or the treatment may be coordinated through a state health department. All children with PKU ideally should be followed by a specialized PKU program with adequate monitoring facilities. Information about the nearest PKU treatment program can be obtained through the state newborn screening program.
Last update: February 2008
National PKU News: www.pkunews.org