Phenylketonuria

• Phenylketonuria (PKU) is a genetic disorder impacting the body’s ability to process phenylalanine.
• Early diagnosis through newborn screening is crucial to prevent severe neurological complications.
• The primary treatment involves a strict, lifelong diet low in phenylalanine.
• Effective management can prevent symptoms and allow individuals to lead healthy lives.
• Regular monitoring and adherence to dietary guidelines are essential for managing PKU.

What is Phenylketonuria (PKU)?

Phenylketonuria (PKU) is an autosomal recessive genetic disorder characterized by the body’s inability to metabolize phenylalanine, an essential amino acid. This condition arises from a deficiency in the enzyme phenylalanine hydroxylase (PAH), which is necessary to convert phenylalanine into tyrosine. Without this enzyme, phenylalanine accumulates in the blood and brain, becoming toxic to the central nervous system.

This accumulation can lead to significant neurological damage if not managed from birth. PKU affects approximately 1 in 10,000 to 15,000 newborns in the United States, according to the Centers for Disease Control and Prevention (CDC). The condition requires lifelong management to prevent severe health complications, primarily through dietary control.

Symptoms, Causes, and Diagnosis of Phenylketonuria

The phenylketonuria symptoms can vary in severity and typically manifest in untreated individuals within the first few months of life. Initially, infants may appear normal, but as phenylalanine builds up, symptoms can include developmental delays, intellectual disability, seizures, behavioral problems, and psychiatric disorders. Other signs might involve a musty odor in the breath, skin, or urine, fair skin and blue eyes (due to phenylalanine’s role in melanin production), and eczema.

The primary phenylketonuria causes are genetic mutations in the PAH gene. These mutations lead to a deficiency or absence of the phenylalanine hydroxylase enzyme. Since PKU is an autosomal recessive disorder, a child must inherit two copies of the mutated gene—one from each parent—to develop the condition. Parents who carry one copy of the mutated gene are typically asymptomatic carriers.

How is phenylketonuria diagnosed? Early diagnosis is critical to prevent irreversible damage. In most developed countries, PKU is identified through routine newborn screening, typically performed within the first few days of life using a heel-prick blood test. This screening measures the level of phenylalanine in the baby’s blood. If the initial screening indicates high phenylalanine levels, further diagnostic tests, such as more detailed blood tests and genetic testing, are conducted to confirm the diagnosis and identify the specific gene mutation.

Phenylketonuria Treatment and Diet Management

The primary phenylketonuria treatment focuses on preventing the accumulation of phenylalanine in the body. This is achieved through a strict, lifelong dietary regimen that limits phenylalanine intake. Early and consistent adherence to this diet is crucial for normal development and to prevent the severe neurological complications associated with untreated PKU.

Phenylketonuria diet management guidelines involve carefully monitoring and restricting foods high in protein, as protein is a significant source of phenylalanine. This typically means avoiding or severely limiting:

• Meat, fish, poultry
• Eggs, dairy products
• Nuts, beans, and other legumes
• Foods containing aspartame (an artificial sweetener that releases phenylalanine)
• Standard bread and pasta

Individuals with PKU must consume specialized medical formulas that provide essential amino acids (excluding phenylalanine) and other vital nutrients. They can also eat carefully measured amounts of certain fruits, vegetables, and low-protein grains. Regular blood tests are performed to monitor phenylalanine levels, and the diet is adjusted as needed, especially during growth spurts, pregnancy, or illness. In some cases, medication such as sapropterin dihydrochloride (Kuvan) may be prescribed to help lower phenylalanine levels in individuals with specific types of PKU who respond to the medication. Adherence to these guidelines, under the supervision of a metabolic dietitian and physician, allows individuals with PKU to lead healthy, productive lives.