Phenylketonuria (PKU) Disease: An Inherited Metabolic Disorder

PKU—How Is This Genetic Disease Inherited?

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Phenylketonuria (fen-ul-keetone-YU-ree-ah, or PKU) is an inherited metabolic disorder where the body cannot completely break down the protein phenylalanine. This happens because a necessary enzyme, phenylalanine hydroxylase, is deficient. Because of this, phenylalanine builds up in the body’s cells and causes nervous system and brain damage.

Phenylketonuria is a treatable disease that can easily be detected by a simple blood test.

In the United States, all newborn babies are required to be tested for PKU. All newborns in the United Kingdom, Canada, Australia, New Zealand, Japan, the nations of Western and most of Eastern Europe, and many other countries throughout the world, are tested as well.

Each year 10,000 to 15,000 babies are born with the disease in the United States and Phenylketonuria occurs in both males and females of all ethnic backgrounds (although it is more common in individuals of Northern European and Native American heritage).

Symptoms of Phenylketonuria

An infant born with phenylketonuria will develop normally for the first few months. If left untreated, symptoms begin to develop by three to six months of age and may include:

  • delayed development
  • mental retardation
  • seizures
  • very dry skin, eczema and rashes
  • distinctive “mousy” or “musty” odor of the urine, breath, and sweat
  • light complexion, light or blonde hair

Diagnosing Phenylketonuria

Phenylketonuria is diagnosed by a blood test, usually as part of the routine screening tests given to a newborn within the first few days of life. If PKU is present, the level of phenylalanine will be higher than normal in the blood.

The test is highly accurate if done when the infant is more than 24 hours old but less than seven days old. If an infant is tested at less than 24 hours old, it is recommended that the test be repeated when the infant is one week old.

Treatment For Phenylketonuria

Because phenylketonuria is a problem of breaking down phenylalanine, the infant is given a special diet that is extremely low in phenylalanine. At first, a special low-phenylalanine infant formula (Lofenalac) is used. As the child grows older, low-phenylalanine foods are added to the diet, but no high-protein foods such as milk, eggs, meat, or fish are allowed. The artificial sweetener aspartame (NutraSweet, Equal) contains phenylalanine, so diet drinks and foods that contain aspartame are also avoided.

Individuals must remain on a phenylalanine-restricted diet during childhood and adolescence. Some individuals are able to reduce their diet restrictions as they grow older. Regular blood tests are needed to measure the levels of phenylalanine, and the diet may need to be adjusted if the levels are too high.

In addition to a restricted diet, some individuals may take the drug Kuvan (sapropterin) to help lower phenylalanine levels in the blood.

How Phenylketonuria Is Inherited

PKU is a genetic disorder that is passed down from parents to children. To have PKU, a baby has to inherit a specific gene mutation for PKU from each parent. If the baby inherits the gene from just one parent, then the baby also carries the gene mutation for PKU, but doesn’t actually have PKU. 

Once PKU is diagnosed in a baby, then that baby must follow a PKU meal plan throughout their whole life. Young women with phenylketonuria who do not eat a phenylalnine-restricted diet will have high levels of phenylalanine when they become pregnant. This can lead to serious medical problems known as PKU syndrome for the child, including mental retardation, low birthweight, heart defects, or other birth defects. However, if the young woman resumes a low-phenylalanine diet at least 3 months prior to pregnancy, and continues on the diet throughout her pregnancy, PKU syndrome can be prevented.

Pending Research

Researchers are looking at ways of correcting phenylketonuria, such as replacing the defective gene responsible for the disorder or creating a genetically-engineered enzyme to replace the deficient one. Scientists are also studying chemical compounds such as tetrahydrobiopterin (BH4) and large neutral amino acids as ways to treat PKU by lowering the level of phenylalanine in the blood.


Van Voorhees, Benjamin. "Medical Encyclopedia: Phenylketonuria." MedlinePlus. National Institutes of Health. Accessed Feb 14, 2016.

Pregnancy & Newborn Health Education Center. PKU (Phenylketonuria) in your Baby. March of Dimes. Accessed Feb 14, 2016.

Michals-Matalon, K. et al. Response of phenylketonuria to tetrahydrobiopterin." Journal of Nutrition 137 (2007): 1564S-1567S.

Matalon, R. et al. "Double blind placebo control trial of large neutral amino acids in treatment of PKU: effect on blood phenylalanine." J Inherit Metab Dis 30(2007): 153-158.

Gambol, P.J. "Maternal phenylketonuria syndrome and case management implications." Journal of Pediatric Nursing 22(2007): 129-138.

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