Phenylketonuria (PKU) is a rare genetic metabolic disorder present from birth, caused by a defect in the PAH gene. This defect prevents the body from producing functional phenylalanine hydroxylase (PAH), an enzyme essential for breaking down phenylalanine, an amino acid found in most protein-containing foods. Without functional PAH, phenylalanine accumulates in the blood and brain to harmful levels. If left untreated, this buildup can interfere with brain development and lead to intellectual disability. Early and consistent lifelong treatment is crucial to prevent these complications.
Dietary Management
The primary treatment for PKU involves a carefully controlled, low-phenylalanine diet. This approach limits phenylalanine intake to prevent harmful accumulation, while still providing enough for normal growth and development. Since phenylalanine is a component of nearly all natural proteins, individuals with PKU must restrict or avoid high-protein foods.
Foods like meat, dairy products, eggs, nuts, and legumes are restricted due to their high phenylalanine content. Even grains like bread and pasta contain phenylalanine and must be managed. Additionally, the artificial sweetener aspartame must be avoided, as it releases phenylalanine when digested.
To compensate for restricted natural protein intake, individuals with PKU rely on specially formulated medical foods, known as protein substitutes or formulas. These products provide essential amino acids, vitamins, and minerals for health, without significant amounts of phenylalanine. Infants with PKU, for example, require a phenylalanine-free infant formula after diagnosis.
Adherence to this diet is important, and food intake often requires measurement to ensure phenylalanine levels remain within a safe range. Dietary needs are individualized, varying based on age, growth rate, and tolerance to phenylalanine. Regular adjustments to the diet are needed throughout life to maintain health.
Medical Therapies
Beyond dietary management, medications offer treatment options for individuals with PKU. These can work with or, in some cases, modify dietary requirements.
One medication is sapropterin dihydrochloride, known as Kuvan. This drug is a synthetic form of tetrahydrobiopterin (BH4), a cofactor required by the PAH enzyme to break down phenylalanine. For some individuals with PKU, especially those with milder forms or specific genetic mutations, Kuvan can enhance the activity of their remaining PAH enzyme. This allows them to process phenylalanine more effectively, potentially leading to a less restrictive diet.
Another option, for adults with uncontrolled phenylalanine levels, is pegvaliase, marketed as Palynziq. This medication is an enzyme substitution therapy that provides an external enzyme to break down phenylalanine in the bloodstream. Palynziq is administered via subcutaneous injection and can reduce phenylalanine levels, potentially allowing adults to consume more protein. However, it can have side effects and requires monitoring.
Ongoing Monitoring and Support
Managing PKU is a continuous process that requires monitoring and support. Regular measurement of blood phenylalanine levels is a key part of this management. These tests are conducted frequently, especially in infancy and childhood, to ensure phenylalanine concentrations remain within the target range. Monitoring helps prevent phenylalanine accumulation to levels that could cause neurological damage.
Individuals with PKU benefit from a multidisciplinary healthcare team. This team includes metabolic specialists who oversee treatment, dietitians who provide nutritional counseling, and genetic counselors who explain the inherited nature of the condition. Psychologists and social workers also offer psychosocial support to individuals and families.
Regular clinic visits are for assessment, dietary adjustments, and medication management. Nutritional counseling helps individuals understand and adhere to their dietary plans, ensuring they receive adequate nutrients and control phenylalanine intake. The support from this team helps individuals with PKU lead healthy lives.
Emerging Treatment Approaches
Research continues to explore new therapies to improve PKU management, offering alternatives or enhancements to current treatments. These emerging approaches aim to address the genetic defect or provide more effective phenylalanine processing.
Gene therapy is one area of research, seeking to introduce a functional PAH gene into the patient’s cells. The goal is to enable the body to produce its own PAH enzyme, correcting the metabolic deficiency. While in investigational stages, this approach holds potential for a long-term solution.
Other therapies under investigation include messenger RNA (mRNA) therapy, which aims to deliver temporary instructions for producing the PAH enzyme. Enzyme replacement strategies are also being explored to develop more efficient ways to introduce the missing enzyme into the body. These advanced treatments are not yet widely available but represent progress in enhancing PKU management.