Alternate Names: PKU

Causes and Risks:

Phenylketonuria (PKU) is inherited as an autosomal recessive trait. Because PKU can be easily detected by a simple blood test and it is a treatable disease, most states require a screening test for all newborns. The genetically determined abnormality in phenylketonuria is a missing enzyme called phenylalanine hydroxylase.

Phenylalanine is one of the eight essential amino acids found in protein-containing foods. In PKU, phenylalanine cannot be used in a normal fashion because of the missing enzyme. Subsequently, high levels of phenylalanine and two closely related phenylalanine derivatives develop. These compounds are toxic to the central nervous system and cause brain damage.

Damage to the brain causes marked mental retardation by the end of the first year of life. Older children may develop movement disorders (athetosis), rocking, and hyperactivity.

Because phenylalanine is involved indirectly in the production of melanin, the pigment responsible for skin and hair color, children with phenylketonuria often have lighter complexions than their unaffected siblings (PKU children often have blond hair and blue eyed).

These children may have an odor described as mouse-like that results from the accumulation of phenylacetic acid. This odor may be detected on their breath, skin, and urine.

Prevention: Genetic counseling is recommended for prospective parents with a family history of phenylketonuria. The carrier state for PKU can be detected by enzyme assays and PKU can be diagnosed prenatally. Screening immediately after birth is done routinely in all U.S. hospitals.

It is imperative that mothers with PKU who becomes pregnant adhere closely to the special low-phenylalanine diet-since accumulation of phenylalanine will damage the unborn baby even if the baby has not inherited the abnormality.

Symptoms:

• Skin rashes (eczema)
• Microcephaly
• Tremors
• Jerking movements of the arms or legs (spasticity)
• Unusual hand posturing
• Seizures
• Hyperactivity
• Delayed mental and social skills
• Mental retardation
• An offensive odor to the urine and sweat ("mousy" odor)
• Light coloration (frequent finding of light complexion, blond hair, and blue eyes)

Signs and Tests: Many children with PKU have a light complexion, blond hair, and blue eyes.

Tests include:

• Enzyme assay to detect the carrier state (parents)
• Chorionic villus sample to detect fetal PKU (prenatal diagnosis)
• PKU screening (a heel-stick blood sample from the infant to screen for PKU; mandatory in most states in the U.S.)

Treatment: Treatment includes a diet that is very low in, or free of, phenylalanine; particularly when the child is growing. Strict compliance to the diet is necessary to reduce or prevent mental retardation. This requires close supervision by a registered dietitian or physician, and cooperation of the parent(s) and child.

Phenylalanine occurs in significant amounts in milk, eggs, and other common foods. Nutrasweet (aspartame) also contains phenylalanine, and products containing aspartame should be avoided for children with this disorder. 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.

Adult women who have PKU and who plan to become pregnant should also adhere to a strict low-phenylalanine diet both before becoming pregnant and throughout the pregnancy.

Prognosis: The outcome is expected to be very good if dietary treatment is followed closely beginning immediately after the child’s birth. If treatment is started after 3 years (or if there is no treatment), brain damage is inevitable.

Complications: Severe mental retardation occurs if the disorder is untreated.

Call your health care provider if your infant has not been tested for PKU. This is particularly important if anyone in your family has the disorder.