From the Guidelines
Phenylketonuria (PKU) is treated primarily through a strict low-phenylalanine diet that begins immediately after diagnosis, ideally through newborn screening, with the goal of maintaining blood phenylalanine levels between 2-6 mg/dL (120-360 μmol/L) throughout life, as recommended by the most recent and highest quality study 1.
Treatment Overview
The treatment for PKU involves a multifaceted approach, including dietary restrictions, supplementation with phenylalanine-free medical formulas, and in some cases, pharmacologic interventions.
- The diet restricts foods high in protein such as meat, dairy, eggs, nuts, and many grains.
- Measured amounts of special low-protein foods and phenylalanine-free medical formulas are allowed to provide necessary nutrients.
- For some patients, the medication sapropterin (Kuvan) at doses of 5-20 mg/kg/day can help by increasing phenylalanine hydroxylase enzyme activity, allowing for a less restrictive diet, as noted in studies 1.
- Another option is pegvaliase (Palynziq), an enzyme therapy administered by subcutaneous injection at 2.5 mg daily initially, gradually increasing to 20-40 mg daily based on response, which breaks down phenylalanine in the blood.
Monitoring and Maintenance
Regular monitoring of blood phenylalanine levels is essential, typically:
- Weekly in infants
- Biweekly in children
- Monthly in stable adults Dietary management must continue throughout life, as elevated phenylalanine levels can cause neurological damage at any age, emphasizing the importance of lifelong treatment and monitoring 1.
Importance of Treatment
Treatment is crucial because phenylalanine accumulation damages the developing brain by interfering with myelin formation and neurotransmitter production, leading to intellectual disability if left untreated. The goal of treatment is not only to reduce phenylalanine levels but also to improve quality of life and prevent long-term neurological and psychiatric complications, as highlighted in the most recent guideline 1.
From the Research
Treatment Overview
The treatment for Phenylketonuria (PKU) primarily involves a low protein diet, supplemented with phenylalanine (Phe)-free protein substitutes and micronutrients 2, 3, 4, 5, 6.
Dietary Intervention
- The diet consists of three parts:
- Severe restriction of dietary Phe
- Replacement of non-Phe l-amino acids with a protein substitute commonly supplemented with essential fatty acids and other micronutrients
- Low-protein foods from fruits, some vegetables, sugars, fats and oil, and special low-protein foods (SLPF) 3
- The use of large neutral amino acids (LNAA) and glycomacropeptides (GMP) has been explored to improve dietary therapy 4, 5, 6
Additional Treatment Strategies
- Slow-release large neutral amino acids (srLNAAs) have been shown to prevent Phe increase following a Phe dietary load 2
- Tetrahydrobiopterin, a cofactor capable of increasing residual activity of phenylalanine hydroxylase, has been used as an addition to treatment 5, 6
- Gene therapy and enzyme replacement or substitution therapy have yielded promising data in recent years 4, 5, 6
- Human trials have been performed with subcutaneous administration of phenylalanine ammonia-lyase, and further efforts are underway to develop an oral therapy containing phenylalanine ammonia-lyase 5, 6