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PKU an update for 2024

What is PKU?

Phenylketonuria (PKU) is a genetic condition that causes elevated levels of an amnio acid called phenylalanine to build up in the body. Phenylalanine is found at high levels in protein-rich foods, such as meat, eggs, and dairy. Phenylketonuria occurs when an enzyme called phenylalanine hydroxylase (PAH), which normally processes phenylalanine, is not functioning properly. If left untreated, PKU can affect a person’s cognitive development. Treatment with medications and/or dietary changes help reduce symptoms.

There are different types of phenylketonuria (PKU) based on the severity of the diagnosis. Symptoms are worse among untreated individuals. Types of PKU include:

  • Classic PKU (most severe)

  • Non-PKU hyperphenylalaninemia (least severe)

In the United States, PKU affects an estimated 1 in every 10,000 to 15,000 newborns annually. Since diagnosis and treatment of PKU most often occur shortly after birth due to an abnormal newborn screen, noticeable symptoms are rare. Symptoms typically affect those with undiagnosed or untreated cases.

Symptoms of untreated PKU include:


  • Eczema

  • Skin and/or hair discoloration

  • Small head size (microcephaly)

  • A musty odor to breath, skin, or urine 

  • Behavioral problems

  • Developmental delay

  • Intellectual disabilities

  • Seizures

The genetics of PKU

PKU is caused by a genetic change passed on by both parents. Parents have 1 normal copy of the gene involved and 1 changed copy; this is called being a “carrier” of the change that causes the disease. To have the condition, the child must inherit a changed phenylalanine hydroxylase gene from each parent. There is a 25% chance this will happen for every child of these parents. This pattern of inheritance is called “autosomal recessive.”

All 50 states test for PKU as part of their newborn screening (NBS) panel. Shortly after birth, a medical provider takes a small blood sample from the baby’s heel to test for PKU, and other conditions. If the NBS is positive for PKU, the baby is referred to a specialist and has further tests to definitively diagnose or rule out PKU. Affected infants can then begin treatment immediately.

Some people have carrier screening for PKU (and often other conditions) prior to or during a pregnancy. If both parents are carriers, prenatal testing is available to diagnose PKU prior to birth. Another option is to have the newborn tested after birth. Individuals found to be a carrier of PKU or have a family history of PKU can benefit from meeting with a genetic counselor.

Treatment for PKU

In PKU, dysfunctional PAH enzyme results in too much phenylalanine and not enough tyrosine. The goal of treatment is to reduce phenylalanine levels in the patient. The ground-breaking, gold-standard treatment developed in the 1950s is dietary intervention. The patient is put on a phenylalanine restricted diet that avoids most natural proteins (and therefore phenylalanine) and phenylalanine-free protein supplements. A phenylalanine-restricted diet remains an important part of treatment for most patients.  However, it’s no longer the only option. The treatment landscape has broadened, allowing a patient and their care team to explore: 

  • Large supplements that decrease phenylalanine transport into the brain. 

  • Therapy with sapropterin that stabilizes or activates an unstable PAH enzyme. 

  • Enzyme substitution therapy with pegvaliase injections, which gives the patient a different working enzyme that can perform some of the same functions as PAH.  

All available treatment approaches have one common goal: to maintain appropriate phenylalanine and tyrosine levels. Through our biochemical genetics’ laboratories, Quest Diagnostics offers testing for plasma phenylalanine and tyrosine levels, as well as broader plasma amino acid panels to assist in the diagnosis and management of patients with PKU.

  • National PKU Alliance.
  • Cleveland Clinic.
  • Lichter-Konecki U, Vockley J. Phenylketonuria: current treatments and future developments. Drugs. 2019;79(5):495-500. doi:10.1007/s40265-019-01079-z 
  • Woolf LI, Adams J. The early history of PKU. Int J Neonatal Screen. 2020;6(3):59. doi:10.3390/ijns6030059


Bonnie Epstein, MA, MS

Cathlin Kučera, MS CGC

Jo Ellyn Taylor, MS CGC