Structural Biochemistry/Phylketonuria (PKU)

Phenylketonuria
Dire consequences result if one or more of amino acids are either absent or overabundant. A genetic disorder called phylketonuria (PKU) is caused by the body’s inability to get rid of extra phenylalanine. PKU is autosomal recessive disorder, meaning that the only way to get the disease is if both of your parents carry a version of a gene linked with this disease. People with PKU are born without the enzyme that breaks down the Phenylalanine amino acid. Extremely high levels of Phe accumulate and are very toxic, especially to the brain as a result, PKU causes mental retardation. Yet Phenylalanine is an essential amino acid—your body cannot do without it. Both diet and genes contribute to causing PKU and so any means to control the supply of Phenylalanine in the body can prevent the disease.

Causes
Phenylketonuria (PKU) is inherited, which means it is passed down through families. Both parents must pass on the defective gene in order for a baby to have the condition. This is called an autosomal recessive trait. Babies with PKU are missing an enzyme called phenylalanine hydroxylase, which is needed to break down an essential amino acid called phenylalanine. The substance is found in foods that contain protein. Without the enzyme, levels of phenylalanine and two closely-related substances build up in the body. These substances are harmful to the central nervous system and cause brain damage.

Symptoms
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.

Other 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
 * If the condition is left untreated or foods containing phenylalanine are not avoided, a "mousy" or "musty" odor may be detected on the breath and skin and in urine. The unusual odor is due to a build up of phenylalanine substances in the body.

Diagnosis
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.

Treatment
However, the silver lining is that the PKU disorder is easy to diagnose and if present, PKU is a treatable disease. Doctors treat children with PKU by prescribing a life-long restrictive diet. Treatment involves a 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 certain foods such as milk, eggs, and diet sodas containing the artificial sweetener aspartame (NutraSweet) are rich sources of Phenylalanine. The diet is rigid requiring people to avoid those and many other foods such as meat and fish, dairy products, bread, nuts, and even some vegetables. As a result, people with PKU have to take a special Phe-free vitamin/mineral supplement to ensure that they receive adequate amounts of all of the other essential amino acids bountiful in those foods. For example, 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. Another example involves taking supplements such as fish oil to replace the long chain fatty acids missing from a standard phenylalanine-free diet in order to help improve neurologic development, including fine motor coordination. Other specific supplements, such as iron or carnitine, may be needed.

Prognosis
The outcome is expected to be very good if the diet is closely followed, starting shortly after the child's birth. If treatment is delayed or the condition remains untreated, brain damage will occur. School functioning may be mildly impaired. If proteins containing phenylalanine are not avoided, PKU can lead to mental retardation by the end of the first year of life. Severe mental retardation occurs if the disorder is untreated. ADHD (attention-deficit hyperactivity disorder) appears to be the most common problem seen in those who do not stick to a very low-phenylalanine diet.

Prevention
An enzyme assay can determine if parents carry the gene for PKU. Chorionic villus sampling can be done during pregnancy to screen the unborn baby for PKU.

It is very important that women with PKU closely follow a strict low-phenylalanine diet both before becoming pregnant and throughout the pregnancy, since build-up of this substance will damage the developing baby even if the child has not inherited the defective gene.