Alternative Names
Deficiency Disease, Phenylalanine Hydroxylase; Folling Disease; Folling's Disease; PAH deficiency; Phenylalanine Hydroxylase Deficiency Disease; PKU
Symptoms & Characteristics
Phenylketonuria, commonly called PKU, is a genetic condition in which the body can't process one of the building blocks of protein called phenylalanine (Phe). Our body can't make Phe, therefore, we must obtain it through food. Phe is essential in the production of another building block called tyrosine (Tyr).
If left untreated, PKU can damage the brain and cause severe mental retardation. The signs and symptoms of PKU vary from mild to severe.
The most severe type of PKU is called classic PKU. If untreated, symptoms may include:
- developmental delay/mental retardation
- musty (or mousy) bodily odor
- fairer skin and hair than other non-affected family members
Less severe types of PKU are called variant PKU and non-PKU hyperphenylalaninemia, and have a smaller risk of brain damage.
Treatment
The best treatment for PKU is a low Phe or low-protein diet, which should begin very soon after birth and continue for the rest of life. There are special formulas for newborns, which are designed to prevent damage. Nutritional formulas for affected children and adults help them get the vitamins and minerals they can't get from food.
Women with PKU, who have uncontrolled, high Phe levels, have an increased risk to have a baby with birth defects as well as complications during pregnancy. It is always important to speak with a doctor regarding the appropriate care and management of PKU before and during pregnancy.
How Common Is It?
About 1 in 10,000 live births are affected with PKU each year in the United States. PKU is most common in Caucasians, especially people of Irish or Turkish descent.
Genetics & Inheritance
PKU is caused by mutations in a gene called PAH at the location12q24.1. The PAH gene is responsible for making an enzyme called phenylalanine hydroxylase, which converts Phe to Tyr. There are about 66 reported mutations and variations of this gene, which all result in varying degrees of reduction in the activity of produced phenylalanine hydroxylase.
- People with no (or very little) phenylalanine hydroxylase activity have classic PKU because Phe cannot be converted and builds up in organs and tissues causing damage.
- People with little phenylalanine hydroxylase activity have variant PKU and non-PKU hyperphenylalaninemia
We have two copies of the PAH gene - one from each parent. It is necessary to have two mutations, one in each gene copy, to be affected. This is called autosomal recessive inheritance.
- Both parents of an affected person are always both obligate carriers (each have only one mutation). Two carriers have a 25% chance with each pregnancy to have an affected child, but do not have symptoms themselves.
- In the absence of a family history, the chance to be a carrier is determined by a person's ethnic background. For example, up to 1 in 50 Caucasians is a carrier of PKU, with people of Irish and Turkish descent at even greater risk.
Other yet to be classified genes may influence PKU symptoms and severity.
A genetic consultation with a trained genetic professional is important for a complete evaluation, accurate diagnosis, as well as discussion of the benefits and limitations of testing and recurrence risk.
Genetic Testing
Clinical genetic testing for PKU can be broken down into two categories: diagnostic testing and carrier testing.
- Diagnostic testing may be used to confirm or rule out a diagnosis in a person suspected to have the disorder. A clinical diagnosis is often made by specific biochemical blood tests.
- Carrier testing is typically offered after a clinical diagnosis and/or mutations have already been identified in an affected family member(s). Carrier testing usually involves DNA testing for the known familial mutations or if not available, the most common mutations. Biochemical testing when used for carrier testing purposes has limitations, but may be used if it is the only option.
Clinical genetic testing for PKU is available through an in person genetic consultation for people who are considered at risk. Use our find a genetic professional directory to locate a trained genetic professional in your area.
All state newborn screening programs include screening for PKU as well.
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