Phenylketonuria (PKU) is an inherited disorder that affects the way the body processes phenylalanine (Phe), an amino acid found in many foods and in some artificial sweeteners.

It is caused by a mutation in the gene that codes for the enzyme phenylalanine hydroxylase (PAH), which is responsible for converting Phe to another amino acid called tyrosine. This results in a build-up of Phe in the blood and brain, which can cause a range of symptoms and complications.

Causes of Phenylketonuria

PKU is caused by a genetic mutation in the PAH gene, which is found on chromosome 12.

This mutation can be inherited in an autosomal recessive pattern, which means that a child must inherit two copies of the mutated gene (one from each parent) in order to develop the condition. If a child inherits only one copy of the mutated gene, they will be a carrier of PKU but will not have the disorder themselves.

There are several types of PKU, depending on the severity of the mutation and the level of Phe in the blood. Classic PKU is the most severe form, and is characterized by a complete absence of PAH activity.

This results in high levels of Phe in the blood, which can cause developmental delays, intellectual disability, seizures, and behavioral problems.

Non-classic PKU is a milder form of the disorder, in which there is some residual PAH activity. This results in lower levels of Phe in the blood and milder symptoms, although some cognitive and behavioral problems may still occur.

Symptoms of Phenylketonuria

The symptoms of PKU can vary depending on the severity of the condition and the level of Phe in the blood. In classic PKU, symptoms may include:.

Developmental delays
Intellectual disability
Seizures
Hyperactivity
Behavioral problems
Musty odor in the breath, skin, and urine

In non-classic PKU, symptoms may include:.

Mild intellectual disability
Behavioral problems
Mild skin rash
Musty odor in the breath, skin, and urine

Diagnosis of Phenylketonuria

PKU is typically diagnosed shortly after birth through a newborn screening test, which measures the level of Phe in the blood. If a high level of Phe is detected, further testing is done to confirm the diagnosis.

In some cases, PKU may not be diagnosed until later in childhood or even adulthood, especially in cases of milder forms of the disorder.

Treatment of Phenylketonuria

The primary treatment for PKU is a strict low-Phe diet, which involves avoiding foods that are high in protein, such as meat, dairy, and certain grains.

Instead, individuals with PKU must rely on special low-protein foods and formula supplements, which are designed to provide essential nutrients without causing a build-up of Phe.

Dietary treatment is most effective when started early in life, ideally within the first few weeks of life. This can help prevent the cognitive and behavioral problems associated with PKU, and allow affected individuals to lead relatively normal lives.

In some cases, medications may be prescribed to help lower Phe levels in the blood.

These include sapropterin dihydrochloride, which is a synthetic form of the enzyme PAH that can help convert Phe to tyrosine, and large neutral amino acid supplements, which can help reduce the absorption of Phe in the intestines.

Prognosis of Phenylketonuria

The prognosis for individuals with PKU varies depending on the severity of the disorder and the level of Phe in the blood.

With appropriate treatment and early intervention, children with PKU can go on to lead relatively normal lives, although they may require ongoing dietary management and monitoring of Phe levels in the blood.

However, if left untreated or poorly managed, PKU can lead to significant cognitive and behavioral problems, including intellectual disability, seizures, and psychiatric disorders such as depression and anxiety.

Prevention of Phenylketonuria

Because PKU is an inherited disorder, it cannot be prevented entirely.

However, genetic counseling and carrier testing can help identify individuals who may be at risk of passing on the mutated gene, and allow them to make informed decisions about family planning.

In addition, early screening and diagnosis of PKU through newborn screening programs can help identify affected infants early in life, allowing them to receive prompt treatment and reducing the risk of long-term complications.

Conclusion

Phenylketonuria is a rare genetic disorder that affects the way the body processes phenylalanine.

Although there is no cure for PKU, early diagnosis and treatment with a low-Phe diet can help prevent the cognitive and behavioral problems associated with the disorder. With ongoing dietary management and monitoring, individuals with PKU can go on to lead relatively normal lives.