May is PKU Awareness Month
By Mary Sowa, MS, RD, CSP, CNSC, CLEC and Jan Skaar, RD, CSP, CNSC, CLE, clinical dietitians at CHOC Children’s
Did you know that one in 10 Americans is living with a rare disease? Phenylketonuria (PKU or PAH) is a rare genetically-inherited disorder that occurs in one in 10,000 to 15,000 newborns in the United States. PKU was the first disorder to be identified at birth by the California Newborn Screening (NBS) program, which now screens for over 70 rare disorders. The main focus for NBS is to detect conditions that can be treated with diet or medications to prevent intellectual and other disabilities. NBS has been identifying babies born with this condition, allowing early treatment and improved outcomes, for five decades. In decades past, treatment options were limited, often resulting in severe intellectual disabilities.
Individuals with PKU are unable to process the amino acid phenylalanine (Phe), which is an essential amino acid found in foods with protein. Children with the “classic” form of PKU need to avoid meat, chicken, fish, eggs, nuts and other foods with high protein content. They may also need to avoid regular breads, pasta, cereals and grains. It is not just a vegetarian diet. Daily intake of a specialized formula, which provides a source of Phe-free protein, vitamins and minerals, is essential for regulating blood Phe levels. Compliance with the specialized formula and low protein food products is the cornerstone to help prevent complications associated with high Phe levels in the brain. Elevated Phe levels can affect school performance, sleep, disposition and executive functioning. Experts recommend that individuals with PKU follow a “Diet for Life.”
“A disorder that is treatable with a special diet?” That must be the end of the story, you might think. Far from it. Besides having more taste-friendly options on the market for specialized PKU formulas, there have been advances in treatment options that were not available to PKU families a couple of decades ago. These include a medication called sapropterin to lower Phe levels in the blood, therapy with large neutral amino acids, and enzyme substitution.
Sapropterin dihydrochloride is a FDA-approved medication that helps the phenylalanine hydroxylase (PAH) enzyme work more effectively to break down Phe in the body. A trial period of close patient monitoring with frequent blood tests is conducted while initiating the sapropterin. Those individuals that are responders to the medication are able to control their blood Phe levels and have a more liberalized protein intake.
For some patients, it may mean the difference between tasting a hamburger or just dreaming about it.
Large neutral amino acids (LNAA) are another treatment option. They are most often used with older teens or adults who have problems controlling their Phe levels with diet or do not respond to the sapropterin. The individual with PKU has a “flood” of Phe in the blood from protein ingestion and the inability to breakdown the Phe into Tyrosine. The LNAA compete with Phe for transporter cells in the GI tract and later transfer across the blood-brain barrier. The LNAAs are considered “safe” amino acids for the brain and reduce the amount of Phe that enters the brain. A decrease in blood Phe levels may not be evident in the blood, however a decrease in brain Phe may help improve the neurocognitive deficits and executive functioning challenges seen in PKU.
In addition, human trials with an enzyme substitute called phenylalanine ammonia lyase (PAL) have been underway as a new treatment option. This is an injectable form of alternate enzyme found in plants and bacteria that can break down Phe into harmless components. The active compound is coated with ethylene glycol to protect it from the body’s immune system or is “pegylated.” The compound known as “PEG-PAL” must be injected daily and has been shown to lower blood Phe levels.
Significant challenges remain for individuals and families with PKU to achieve and maintain optimal blood Phe control and improved health outcomes. However, there are many more available tools for success than in previous years. Gene therapy is also a potential option on the horizon.
The CHOC Metabolic Clinic team, under the direction of Dr. Jose Abdenur, consists of dedicated staff to help patients with PKU and their families adhere to “diet for life” and other therapies. The team provides ongoing treatment, support and education for our PKU families and includes dietitians with specialized training in medical nutrition therapy for PKU and a variety of other metabolic disorders.