What is PKU?

Phenylkentonuria (PKU) is an inherited genetic disorder whereby the body is unable to process an important amino acid called phenylalanine. Normally, a specific enzyme called phenylalanine hydroxylase (PAH) converts phenylalanine into a different type of amino acid called tyrosine. Because the PAH enzyme is not functional in those suffering from PKU a build up of phenylalanine (Phe) will occur within the body (1).

Signs & Symptoms

Untreated children who have PKU are normal at birth. However too much Phe is toxic to the brain and can lead to vomiting, irritability, seizures and behavioral problems. By 1 year of age they have obvious signs of developmental delay. They may also have a musty odor and dry skin. In terms of colouring, Phe is involved in melanin production, which is responsible for skin and hair colour. Therefore, children suffering from Phe tend to have lighter hair, eyes and skin colour than their siblings without the disease (1, 2).

How do you get PKU?

Because PKU is a genetic disorder it is important to first learn a bit about genetics, then we can understand how this disorder is passed on. The term genetics refers to genes in the body which carry all different types of information from physical appearance like hair colour, eye colour and height to instructions on proper body function like making PAH and other enzymes. Genes always come in pairs; one gene comes from your mother and the other from your father. Now there are two categories of genes: Dominant and Recessive. A gene is dominant when it only needs a minimum of one gene (either from your mom or dad) to have an effect. A gene is recessive when it needs two genes to have an effect. In this case, PKU is a recessive inherited genetic disorder so it requires two abnormal PAH genes; one from each parent (3).

There are 3 types of possible outcomes in a recessive genetic disease:

  1. A person has 2 normal PAH genes = Does not have PKU
  2. A person has 1 normal PAH gene and 1 abnormal PAH gene = Carries PKU but does not have PKU
  3. A person has 2 abnormal PAH genes = Has PKU

In the picture below both parents are carriers of PKU (but do not have PKU). These are the possible outcomes they would have if they had children.

Here the parents both carry the abnormal PAH gene, so they have a 25% chance of having a child with PKU (rr), a 50% chance of having a child who carries PKU (Rr) and a 25% chance of having a child without PKU (RR).

It is important to note that parents of children with PKU should not feel guilty or to blame as we all are carriers for many different types of abnormal genes and we only find out when a disease appears.

The best way to monitor or predict PKU is through family history.

How are babies tested for PKU?

All babies in Canada and the United States are tested in the first few days of birth. The test consists of poking the the babies foot to draw blood. The blood is then tested to see if there are abnormally high levels of phenylalanine (Phe). If the result come back and the newborn has higher then expected level of Phe , the doctor will perform other tests to see if the baby has PKU (4).


(5) Paul, D. (2000)

PKU Statistics

Currently the number of new cases annually in America is 1 in 10,000-13,500 births (6).

Figure 3

Treatment/Management

The best way to treat or manage PKU is through diet. It is best to control the amount of Phe in your diet by reducing protein found in meat, eggs, nuts, dairy, fish and other high protein foods. High concentrations of Phe are also found in artificial sweeteners (Equal and Nutrasweet), so they too must be avoided.

Many studies have proven that diet is the best management strategy and should be continued through out life. In the past health care professionals thought that strict diets could be safely discontinued at the age of 6 when the brain is fully developed. However, recent studies showed that not continuing the diet into later years resulted in decreased IQ, learning disabilities and behavioral problems (6, 7).

There is no set PKU diet that will work for everyone, the amount of Phe the body can handle varies from person to person. It is extremely important for those suffering from PKU to go for regular blood tests with a physician and work collaboratively with a dietician to build a personalized program that will work for you.

References

  1. Meglio, D. G. (1998). Phenylketonuria. Pediatrics in Review, 19, 213-216.
  2. Bodamer, A. O., (2008). Overview of Phenylketonuria. Retrieved October 20th, 2008 from UpToDate Website
  3. Scriver, C. R., Kaufman, S. (2001). The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill Publishing
  4. Kaye, C. I., &Committee on Genetics (2006). Newborn Screening Fact Sheets. Pediatrics, 118, 934-963
  5. Paul, D. (2000). A double edged sword :The technical fix for one genetic disorder had unforeseen repercussions. Nature, 405, 515-516.
  6. National Institutes of Health Consensus Development Conference Statement: phenylketonuria: screening and management. (2001). Pediatrics, 108, 972-978.
  7. Mitchell, J.J., & Scriver, C.R. (2000). Phenylalanine Hydroxylase Deficiency. Retrieved October 24th, 2008 from NCBI Website