Phenylketonuria (PKU) is a rare, inherited metabolic disorder that is characterized by the inability of the body to utilize the essential amino acid, phenylalanine (Phe). Amino acids, usually obtained from the food we eat, are the building blocks for body proteins. PKU is caused by a deficiency of the liver produced enzyme phenylalanine hydroxylase (PAH).

This enzyme normally converts Phe to another amino acid, tyrosine. Without this enzyme, Phe accumulates in the blood and body tissues. Excess Phe is toxic to the central nervous system and causes the severe problems normally associated with PKU. When left untreated, PKU patients who consume too much Phe are at risk of severe neurological complications, including IQ loss, memory loss, concentration problems, mood disorders, and in some cases, severe mental retardation.

Damage done is irreversible so early detection is crucial. When treatment is begun early (within the first few weeks of life) and rigorously adhered to, affected children can expect normal development and a normal life span. PKU can be treated by a diet low in phenylalanine and high in tyrosine. While there is no cure, in recent years a few drug products have become available that can be used in limited cases to mitigate the effects of the disorder. Other therapies currently under investigation include an injectable form of PAH and gene therapy.


The gene defect for PKU is an autosomal recessive genetic defect and is unknowingly passed down from generation to generation. This means an affected person inherited two genetic defects for the disorder (one from each parent). A person with one genetic defect for the disorder, is called a 'carrier' for PKU. Carriers do not have symptoms of the disorder. When two carriers conceive a child, there is a one in four (or 25%) chance for each pregnancy that the baby will have PKU. The incidence of carriers in the general population is approximately one in fifty people, but the chance that two carriers will mate is only one in 2500.[2] Carrier testing for PKU is available through several commercial testing companies. If you would like more information about genetic testing for PKU, speak with your doctor or a genetic counselor.

Classical PKU affects between 1 in 10,000 and 1 in 20,000 depending on the country of origin. The incidence varies widely in different human populations from 1 in 4,500 births among the population of Ireland[3] to fewer than one in 100,000 births among the population of Finland.[4] Even higher levels have been reported in the Eastern Mediterranean region (1 in 4,000 in Turkey and 1 in 3,627 in the Islamic Republic of Iran).[5] Poland and the Czech Republic also reportedly have high incidence rates. In the US the incidence rate appears to be about 1 in 12,000 to 1 in 20,000 for Caucasians and Asians. The NPKUA estimates there are currently 16,500 people living with PKU in the United States. There is no difference in frequency of occurrence between males and females .[6]


Newborns affected by PKU usually do not show any signs of the disease at birth. But within the first few weeks of life they begin to show neurologic disturbances such as epilepsy. Children suffering from undiagnosed PKU also may have a "musty or mousy" odor of skin, hair, sweat and urine (due to phenylacetate accumulation). It has been shown that almost 90% of affected people have light coloration such as blond hair and blue eyes. Signs also include skeletal changes such as a small head, short stature, and flat feet. PKU sufferers may also exhibit skin disorder ( eczema). tremors, jerking movements of the arms or legs, and unusual hand posturing. Hyperactivity, EEG abnormalities,  seizures, and severe learning disabilities are major clinical problems later in life. If left untreated, the child is likely to experience behavior problems and developmental delays. Severe brain problems may occur such as mental retardation.

The initiation of screening in the mid-1960’s throughout the US of all newborns has resulted in the early identification and treatment of PKU affected children with very successful results. The several hundred babies diagnosed each year and placed on diet are growing up normally. They are attending college and becoming productive adults as doctors, lawyers, teachers and engineers because of early diagnosis and strict treatment.[7]

Usually children are tested at least 12 hours and generally 24–28 hours after birth[8], using a blood sample drawn from the heel of the foot.


Newborn screening allows early identification and early implementation of treatment. The goal of PKU treatment is to maintain the blood level of Phe between 2 and 6 mg/dl[9]. Some Phe is needed for normal growth. This requires a diet that has some Phe but in much lower amounts than normal. High protein foods such as: meat, fish, poultry, eggs, cheese, milk, dried beans, and peas are avoided. Instead, measured amounts of cereals, starches, fruits, and vegetables, along with a milk substitute are usually recommended. These foods are allowed in quantities that suit the individual child's tolerance for Phe; some can have fairly liberal diets and still maintain good control of blood phe, while others must have a very strict diet. A synthetic, Phe free formula is used as a nutritional substitute for the eliminated foods. Formulas are available for all age groups.

Previously, PKU affected individuals were allowed to go off diet after approximately 6 to 12 years of age. Now treatment is for life, in order to promote maximal development and cognitive abilities. Trying to reinstitute the PKU diet after a period of 'relaxation' to a regular diet, has been difficult for many individuals. Periodic Phe blood level measurement, and the guidance of a nutritionist and other members of the health care team, allow individuals and families to work toward consistently maintaining the blood level in the desirable range.

In just the past few years two new products have become available for persons with PKU. Kuvan, a prescription drug, causes residual enzyme activity to work harder to reduce blood Phe levels and has been effective in reducing blook Phe levels in some people with PKU. Another new product with limited application are large neutral amino acides (LNAA's) which work by blocking Phe uptake through the digestive tract.


For women affected with PKU, it is essential for the health of their child to maintain low Phe levels before and during pregnancy. Women with PKU who have high levels of Phe in their blood have a very large probability of harming their unborn baby. Though the developing fetus may only be a carrier of the PKU gene, the intrauterine environment can have very high levels of Phe, which can cross the placenta. The result is that the child may develop congenital heart disease, growth retardation, microcephaly and mental retardation. PKU-affected women themselves are not at risk from additional complications during pregnancy.

Women of child bearing age who were once on but later went off the diet, are now being seen in greater numbers. This situation poses high risks and it is important that these women recognize the special needs they have for dealing with conception and pregnancy.  The best observed outcomes occur when strict control of the maternal blood Phe level is instituted before conception and continued throughout pregnancy.

An ongoing international study has shown that returning the woman to diet before conception and keeping blood Phe levels below 6 mg/dl results in the best outcome for the baby[10]. The currently recommended Phe levels of control during pregnancy are at least as strict, if not more strict, than that currently recommended for PKU treatment during early childhood. Many children born to mothers with PKU are developing normally because of early and strict treatment.

  1. http://www.shs-nutrition.com/conditions/phenylketonuria-PKU?gclid=CJu6kpSc25oCFRJdxwodFh4xGA
  2. http://www.pkunews.org/about/intro.htm
  3. DiLella, A. G., Kwok, S. C. M., Ledley, F. D., Marvit, J., Woo, S. L. C. (1986). "Molecular structure and polymorphic map of the human phenylalanine hydroxylase gene". Biochemistry 25: 743–749.
  4. Guldberg, P., Henriksen, K. F., Sipila, I., Guttler, F., de la Chapelle, A. (1995). "Phenylketonuria in a low incidence population: molecular characterization of mutations in Finland". J. Med. Genet 32: 976–978.
  5. http://www.shs-nutrition.com/conditions/phenylketonuria-PKU?gclid=CJu6kpSc25oCFRJdxwodFh4xGA
  6. http://www.medhelp.org/lib/pku.htm
  7. http://www.pkunews.org/about/intro.htm
  8. http://en.wikipedia.org/wiki/Phenylketonuria
  9. http://www.medhelp.org/lib/pku.htm
  10. Maternal Phenylketonuria Policy Statement, Pediatrics Vol.107 No. 2 (Feb 2001) pp 427-428, American Academy of Pediatrics