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Sunday, 15 August 2004
Sunday, 15 August 2004
PKU, Phenylalanine Hydroxylase (PAH) Deficiency,Hyperphenylalaninemia


Individuals with phenylketonuria (PKU) lack an enzyme that helps break down the amino acid phenylalanine. Amino acids are substances that form proteins in our cells. Since these individuals lack this enzyme, phenylalanine builds up in their blood. High levels of phenylalanine in the blood can affect brain development and cause severe mental retardation, along with other effects in the body. Fortunately, if this disease is identified early in newborns and treated quickly with a special diet, many of the effects of phenylalanine hydroxylase (PAH) deficiency, such as mental retardation, can be avoided.


PKU occurs in about 1 in 10,000 live births in the US and occurs equally in males and females. It is found in all ethnicities worldwide, but occurs at higher rates in individuals of Caucasian and Asian ancestry. PKU is an autosomal recessive type of genetic disease. This means that both parents carry at least one altered copy of the gene for the PAH enzyme, and that the affected child inherited two nonfunctioning copies, one from each parent. Individuals with one broken copy and one normal copy do not have the disease or any of its symptoms, but are called carriers because the broken copy can be passed on genetically to their children. In a family where both parents are carriers, their children have a one in four chance of having the disease.

Signs and Symptoms

Since newborns with PKU usually do not show any signs and symptoms, special tests may be done to check for high phenylalanine levels in the blood. If PKU is not detected early enough and treated quickly, it leads to sustained, high phenylalanine levels in the blood. This can cause brain damage and mental retardation. Around 3-6 months, untreated infants can start showing changes, such as decreased interest in their surroundings and in reduced activity levels. By 1 year they can show signs of developmental delay, and be irritable and restless. Individuals with PKU may also have dry skin, seizures (due to abnormal electrical activity in the brain), changes in their skin and hair coloration, rashes similar to eczema (with itchiness, redness, and blistering), and may have a “musty” odor because of the high phenylalanine levels in the sweat and urine. They may also have other learning disabilities, behavioral problems, and changes in their movements like the way they stand and walk.

Possible Causes

Genes are important in forming proteins. If a gene is altered, the protein from it may not work properly or there may not be enough of the protein. Since individuals with PKU have two defective copies of the PAH gene, the PAH enzyme is inadequate. This enzyme normally helps break down the amino acid phenylalanine. Since individuals with PKU don’t have enough of the working enzyme, the amount of phenylalanine in their blood is high, which causes their signs and symptoms. Many different mutations of the PAH gene have been found and the disease is often categorized into 3 types, called classic phenylketonuria (PKU), non-PKU hyperphenylalanemia (HPA), and variant PKU. In classic phenylketonuria (PKU), there is either a complete lack or almost complete lack of the PAH enzyme. So individuals with this type of PKU often have a severer form of the disease compared to other types, and have higher levels of phenylalanine in their blood. In the other two types of PKU, individuals have more of the PAH enzyme compared to those with classic PKU and so have a less severe form of the disease.


All states in the US perform screening tests for PKU in newborn infants born in hospitals. Parents of babies born at home are advised to have their babies tested within 2 days. These tests can detect high phenylalanine levels in the blood. This screening is done by collecting a small amount of blood from the infant’s heel and allowing it to dry on filter paper. The dried blood can then be tested in a state laboratory. If a newborn is found to have high phenylalanine, more tests will be done to check and confirm the results. If a baby is diagnosed with PKU, the amount of phenylalanine in the blood can help identify which type of PKU is present which then affects the plan for treatment.


The main treatment for classic PKU is a special diet that has very little or no phenylalanine. The main goal of the treatment plan is to make sure that the blood levels of phenylalanine stay in a safe range and is not too high. If the blood levels stay in a safe range, many of the signs and symptoms of PKU can be avoided. The infant may be given a special formula first that is high in protein but has no phenylalanine, since proteins are important for the body. Later on, foods that are low in phenylalanine may be added to the diet, and an individualized diet can be made for each person with PKU, depending on his or her age, weight, and the amount of phenylalanine in the blood. Following the recommended diet is very important for individuals with PKU. In prior years, doctors recommended maintaining the no or low phenylalanine diet throughout childhood and adolescence. Some doctors are now recommending that individuals with PKU stay on diet throughout their lifetime, since this may continue to help prevent changes in mental and cognitive activities. The treatment plan for individuals with types of PAH deficiency other then PKU can vary, depending on their blood levels of phenylalanine.


Early identification and treatment of PAH deficiency, and maintaining the recommended diet, usually has a good prognosis for patients, and helps prevent the severe effects of PKU like mental retardation. For women with PKU who are planning to have children, the PKU diet needs to be started before pregnancy and continued during pregnancy to avoid having high phenylalanine levels in the blood, which can affect the developing baby.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.


National PKU News
This is a great website that offers educational resources, information on formulas/foods for PKU, additional web-links, and support groups for families. Children's PKU Network Phone: 1-800-377-6677; 1-858-509-0767
This network provides an “express packet” of information for parents with child recently diagnosed with PKU. They also provide additional educational resources, financial aid for families, and have lists of formula/food suppliers. March of Dimes Birth Defects Foundation Phone: 1-888-MODIMES (1-888-663-4637)
This website offers a very informative and parent-friendly summary on PAH deficiency.

National Library of Medicine Genetics Home Reference
This website has summary of PKU facts plus many web-links to additional resources.

PAH/PKU Knowledgebase
This website mainly has information genetic mutations and PKU, but under the “websites” link on the homepage, you can access a list of other web-links that have very helpful informational and support resources.

University of Washington
This website has a general summary on PKU plus more specific information on the PKU diet.

The Arc (a national organization on mental retardation)
This organization has specific chapters in different locations and the website has many links that may have helpful resources for individuals with mental retardation or learning disabilities.

Google Search for Phenylketonuria

References and Sources