Phenylketonuria

Phenylketonuria
Other names	PKU
Specialty	Genetics, Pediatrics
Symptoms	Intellectual disability, seizures, behavioral problems, mental disorders
Usual onset	Early infancy
Duration	Lifelong
Causes	Genetic (autosomal recessive inheritance)
Risk factors	Family history
Diagnostic method	Newborn screening (blood test)
Treatment	Low-phenylalanine diet, Amino acid supplements
Medication	Sapropterin
Prognosis	Good with early treatment
Frequency	1 in 10,000 to 15,000 newborns in the United States

Phenylketonuria (PKU) is a genetic disorder characterized by an inability in the body to metabolize the amino acid phenylalanine. Due to a deficiency in the enzyme phenylalanine hydroxylase, individuals with PKU accumulate high levels of phenylalanine in their blood, which can lead to various health problems including intellectual disability, seizures, and other serious medical issues.

Causes

PKU is caused by mutations in the PAH gene, which encodes the enzyme phenylalanine hydroxylase. This enzyme is crucial for the normal metabolism of phenylalanine, a building block of proteins. The mutations lead to reduced activity or complete absence of this enzyme, resulting in the accumulation of phenylalanine. PKU is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected.

Symptoms

The primary symptoms of PKU include:

• Intellectual disability
• Seizures
• Delayed development
• Behavioral problems
• Psychiatric disorders
• Skin rashes (eczema)

If the disorder is not diagnosed early, and dietary management is not initiated, the buildup of phenylalanine can impair brain development leading to progressive intellectual disability and other neurological issues.

Diagnosis

PKU is commonly diagnosed through newborn screening, which involves a simple blood test to measure phenylalanine levels. This test is typically performed within a few days of birth. Early diagnosis and treatment are crucial to prevent the symptoms and complications associated with PKU.

Treatment

The main treatment for PKU involves a diet low in phenylalanine, which necessitates strict dietary management to limit the intake of foods high in this amino acid, such as meat, fish, eggs, and dairy products. Special low-phenylalanine formulas and foods are used to support normal growth and development in children.

Additionally, some individuals may benefit from the drug sapropterin (a synthetic form of tetrahydrobiopterin or BH4), which can increase the tolerance to phenylalanine in some cases. Regular monitoring of phenylalanine levels in the blood is necessary to adjust dietary intake and ensure optimal management.

Prognosis

With early and consistent treatment, individuals with PKU can lead healthy lives with normal intelligence. Ongoing research continues to explore new treatments and potential cures, including gene therapy.

Epidemiology

The incidence of PKU varies globally, but it is estimated to affect approximately 1 in 10,000 to 15,000 newborns in the United States. It is more common in certain populations, such as those of European descent.