Alternative names

Phenylketonuria (PKU) is a rare hereditary condition in which the amino acid phenylalanine is not properly metabolized. PKU can cause severe mental retardation if not treated.

Causes, incidence, and risk factors

Phenylketonuria (PKU) is inherited as an autosomal recessive trait (both parents must pass on the defective gene for the child to be affected). The genetically-determined abnormality in phenylketonuria is a missing enzyme called phenylalanine hydroxylase.

Phenylalanine is 1 of the 8 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 2 closely-related phenylalanine derivatives, build up in the body. 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 if the offending proteins are not scrupulously avoided. Older children may develop movement disorders (athetosis), rocking, and hyperactivity.

PKU is a treatable disease that can be easily detected by a simple blood test. Most states require a screening test for all newborns, generally done with a heelstick shortly after birth.

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. There is a characteristic “mousy” odor that results from the accumulation of phenylacetic acid. This odor may be detected on the breath, skin, and urine if the condition has not been treated immediately from birth or if foods containing phenylalanine are consumed.


  • 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  
  • A distinctive “mousy” odor to the urine and sweat  
  • Light coloration (frequent finding of light complexion, blond hair, and blue eyes)

Signs and tests

Tests include:

  • Enzyme assay to detect the carrier state (parents)  
  • Chorionic villus sample to detect fetal PKU (prenatal diagnosis)  
  • PKU screening (a heelstick blood sample from the infant to screen for PKU, mandatory in most states)

Treatment includes a diet that is extremely low in phenylalanine, particularly when the child is growing. Strict compliance to the diet is necessary to prevent or minimize mental retardation. This requires close supervision by a registered dietitian or physician, and cooperation of the parent 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 by 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.

Expectations (prognosis)
The outcome is expected to be very good if dietary treatment is followed closely beginning shortly after the child’s birth. If treatment is started after 3 years, or if the disorder remains untreated, brain damage is inevitable.

Severe mental retardation occurs if the disorder is untreated. ADHD (attention-deficit hyperactivity disorder) appears to be the most common problem seen in children - and, perhaps, adults - who do not adhere to a very low-phenylalanine diet.

Calling your health care provider
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.


Genetic counseling is recommended for prospective parents with a family history of PKU. The carrier state for PKU can be detected by enzyme assays, and PKU can be diagnosed prenatally.

It is imperative that a woman with PKU who becomes pregnant adheres 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.

Johns Hopkins patient information

Last revised: December 3, 2012
by Levon Ter-Markosyan, D.M.D.

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