Phenylketonuria
What is phenylketonuria?
Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the blood levels of a substance called phenylalanine. Phenylalanine is an amino acid (a building block of proteins) that is obtained through the diet. It is found in all proteins and in some artificial sweeteners. If PKU is not treated, excess phenylalanine can build up to harmful levels in the body, causing mental retardation and other serious health problems.
The signs and symptoms of this genetic disorder vary from mild to severe. The most severe form of this disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old. Without treatment with a special low-phenylalanine diet, these children develop permanent mental retardation and behavioral problems. Seizures, delayed development, and movement disorders are also common. Affected individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body. Children with classic PKU tend to have lighter skin and hair than unaffected family members and are also likely to have skin disorders such as eczema.
Less severe forms of PKU metabolism disorder (sometimes called moderate or mild PKU) have a smaller risk of brain damage. People with very mild cases may not require a special treatment diet.
Babies born to mothers with high levels of phenylalanine have a significant risk of mental retardation because they are exposed to very high levels of phenylalanine before birth. These infants may also grow more slowly than other children. Other characteristic medical problems include heart defects or other heart problems, small head size (microcephaly), and behavioral problems. Women with PKU metabolism disorder and uncontrolled phenylalanine levels also have an increased risk of pregnancy loss.
How common is phenylketonuria?
Most cases of PKU genetic disorders are detected by newborn screening and treatment is started promptly. As a result, the severe signs and symptoms of classic PKU are rarely seen.
The occurrence of PKU metabolism disorder varies among ethnic groups and geographic regions worldwide. In the United States, PKU is detected in 1 in 10,000 to 15,000 newborns.
What genes are related to phenylketonuria?
Mutations in the PAH gene cause phenylketonuria.
The PAH gene produces an enzyme called phenylalanine hydroxylase, which converts the amino acid phenylalanine to other essential compounds in the body. Normal levels of this amino acid are important for brain function. If gene mutations reduce the activity of phenylalanine hydroxylase, phenylalanine from the diet can build up to toxic levels in the bloodstream and other tissues. Excess phenylalanine damages nerve cells, resulting in brain damage.
Classic PKU, the most severe form of the metabolism disorder, occurs when phenylalanine hydroxylase activity is severely reduced or absent. As a result, people with untreated classic PKU have very high levels of phenylalanine that cause brain damage. Mutations in the PAH gene that allow some enzyme activity cause mild or moderate forms of PKU.
How do people inherit phenylketonuria?
This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the genetic disorder.
Information Obtained From National Institute Of Health