Description, Causes and Risk Factors:

Abbreviation: PKU

Autosomal recessively inherited inborn error of metabolism of phenylalanine characterized by deficiency of (1) phenylalanine hydroxylase caused by mutation in the phenylalanine hydroxylase gene (PAH) on 12q; (2) occasionally, dihydropteridine reductase, caused by mutation in the dihydropteridine reductase gene (DHPR) on 4p; (3) rarely, dihydrobiopterin synthetase, caused by mutation in the pyruvoyl tetrahydropterin synthase gene (PTS) on 11q; or (4) even more rarely, guanidine triphosphate cyclohydrolase 1. The disorder is characterized by inadequate formation of L-tyrosine, elevation of serum L-phenylalanine, urinary excretion of phenylpyruvic acid and other derivatives, and accumulation of phenylalanine and its metabolites, which can produce brain damage resulting in severe mental retardation, often with seizures, other neurologic abnormalities such as retarded myelination and deficient melanin formation leading to hypopigmentation of the skin and eczema.

Phenylketonuria is the most common disorder of amino acid metabolism affecting the PAH gene, which encodes for the enzyme phenylalanine hydroxylase. This defect results in toxic hyperphenylalanemia from a breakdown in the hydroxylation of phenylalanine (Phe) to tyrosine, the first step in the catabolic metabolism of Phe. This defect causes the symptoms of PKU, which include profound mental retardation and progressive motor dysfunction, which arise from gross imbalances in central nervous system (CNS) metabolism.

PKU is a genetic condition caused by a change in the PAH (Phenylalanine Hydroxylase) gene. The PAH gene is responsible for making an enzyme called phenylalanine hydroxylase. Phenylalanine hydroxylase changes phenylalanine to other needed compounds in the body. When there is an alteration in the PAH gene, phenylalanine hydroxylase levels go down; therefore, phenylalanine builds up in the blood stream.

PKU is inherited in an autosomal recessive pattern, which means two copies of the PAH gene must be changed for a person to be affected with PKU. Most often, the parents of a child with an autosomal recessive condition are not affected because they are “carriers”, with one copy of the changed gene and one copy of the normal gene.

When both parents are carriers, there is a one-in-four (or 25 percent) chance that both will pass the changed PAH gene on to a child, causing the child to be born with the condition. There also is a one-in-four (or 25%) chance that they will each pass on a normal PAH gene, and the child will be free of the condition. There is a two-in-four (or 50%) chance that a child will inherit a changed PAH gene from one parent and a normal PAH gene from the other, making it a carrier like its parents. These chances are the same in each pregnancy with the same parents.

Maternal PKU is when there are high levels of phenylalanine in a woman's blood during pregnancy. This circulates to the growing fetus. These high levels greatly increase the risk for a baby to be born with a small head size (microcephaly), mental retardation, growth delay, heart defects, characteristic facial features and behavioral problems. For women with PKU, it is important that they follow a low phenylalanine diet if they plan to become pregnant or are pregnant. The bad effects of high levels of phenylalanine can be prevented if this diet is followed prior to conception and during the pregnancy.

The occurrence of PKU varies among ethnic groups and geographic regions worldwide. In the United States, PKU occurs in 1 in 10,000 to 15,000 newborns. Most cases of PKU are detected shortly after birth by newborn screening, and treatment is started promptly. As a result, the severe signs and symptoms of classic PKU are rarely seen.


The signs and symptoms of PKU vary from mild to severe.General symptoms may include:

    Delayed mental and social skills.

  • Head size significantly below normal.

  • Hyperactivity.

  • Jerking movements of the arms or legs.

  • Mental retardation.

  • Seizures.

  • Skin rashes.

  • Tremors.

  • Unusual positioning of hands.

The most severe form of this disorder is known as classic PKU.

    Infants with classic PKU appear normal until they are a few months old.These infants may also have a low birth weight and grow more slowly than other children.Other characteristic medical problems include heart defects or other heart problems, an abnormally small head size (microcephaly), and behavioral problems.

  • Seizures, delayed development, behavioral problems, and psychiatric disorders are also common.

  • Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body.

  • Children with classic PKU tend to have lighter skin and hair than unaffected family members and are also likely to have skin disorders such as eczema.

  • Phenylalanine plays a role in the body's production of melanin, the pigment responsible for skin and hair color. Therefore, infants with the condition often have lighter skin, hair, and eyes than brothers or sisters without the disease.


PKU can be easily detected with a simple blood test. All states in the US require a PKU screening test for all newborns as part of the newborn screening panel. The test is generally done by taking a few drops of blood from the baby before the baby leaves the hospital.If the initial screening test is positive, further blood and urine tests are required to confirm the diagnosis.


The main goal of PKU treatment is to maintain safe blood phenylalanine concentrations to correct the inborn metabolic imbalance, thereby preventing mental retardation and promoting normal physical growth and development, as well as a healthy lifestyle through to adolescence and beyond. Clinicians commonly advocate phenylalanine concentrations of 2-6mg/dL (120-360µM) for patients up to 12 years of age and 2-10mg/dL (120-600µM) for patients over 12 years of age. These concentrations can be achieved by introduction of a low-phenylalanine diet; this is the mainstay of PKU treatment to which all patients with classic PKU will respond.

PKU Diet: Diet that is extremely low in phenylalanine, particularly when the child is growing. The diet must be strictly followed. This requires close supervision by a registered dietitian or doctor, and cooperation of the parent and child. Those who continue the diet into adulthood have better physical and mental health. “Diet for life” has become the standard recommended by most experts. This is especially important before conception and throughout pregnancy.

Phenylalanine occurs in significant amounts in milk, eggs, and other common foods. The artificial sweetener NutraSweet (aspartame) also contains phenylalanine. Any products containing aspartame should be avoided.

A special infant formula called Lofenalac is made for infants with PKU. It can be used throughout life as a protein source that is extremely low in phenylalanine and balanced for the remaining essential amino acids.

Taking supplements such as fish oil to replace the long chain fatty acids missing from a standard phenylalanine-free diet may help improve neurologic development, including fine motor coordination. Other specific supplements, such as iron or carnitine, may be needed.

NOTE: The above information is for processing purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.


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