Understanding PKU

Phenylketonuria (PKU) is an inherited disorder that increases the level of phenylalanine (Phe), an amino acid, in the blood.[MedlinePlus] source: MedlinePlus Genetics: Phenylketonuria (NIH) (opens in a new tab) It is caused by variants in the PAH gene, which provides instructions for the enzyme phenylalanine hydroxylase. That enzyme normally converts phenylalanine into other important compounds; in PKU it does not work properly, so the body cannot efficiently process Phe.[MedlinePlus] source: MedlinePlus Medical Encyclopedia: Phenylketonuria (NIH) (opens in a new tab)[NPKUA] source: National PKU Alliance: About PKU (opens in a new tab)

PKU is inherited in an autosomal recessive pattern: a child has PKU when they inherit a variant in both copies of the gene.[MedlinePlus] source: MedlinePlus Genetics: Phenylketonuria (NIH) (opens in a new tab) If PKU is not treated, Phe can build up to harmful levels, causing intellectual disability and other serious health problems.[MedlinePlus] source: MedlinePlus Genetics: Phenylketonuria (NIH) (opens in a new tab)

Most cases of PKU are detected shortly after birth by newborn screening, so treatment can start promptly.[MedlinePlus] source: MedlinePlus Genetics: Phenylketonuria (NIH) (opens in a new tab) All U.S. states require a PKU screening test for newborns as part of the newborn screening panel.[MedlinePlus] source: MedlinePlus Medical Encyclopedia: Phenylketonuria (NIH) (opens in a new tab)

For the screen, a health professional takes a few drops of blood from the baby's heel and places them on a filter paper card.[CDC] source: CDC: About Newborn Screening (opens in a new tab) PKU was the first inborn error of metabolism to be identified through population screening.[ACMG] source: ACMG guideline: Vockley et al., Genet Med 2014 (PubMed 24385074) (opens in a new tab)

Too much Phe can cause neurologic injury, while too little can lead to protein malnutrition, so the diet has to be carefully balanced. That balance depends on tracking blood Phe levels, which fluctuate throughout the day.[NSF] source: NSF SBIR Phase I award #2051803 abstract (opens in a new tab)

Today, laboratory test results typically take 5 to 7 days, and sometimes longer.[NSF] source: NSF SBIR Phase I award #2051803 abstract (opens in a new tab) Testing intervals of 3 to 5 days, or even up to two weeks, are common, constrained by test sites, facility availability, and turnaround times.[NSF] source: NSF SBIR Phase II award #2332518 abstract (opens in a new tab)

The American College of Medical Genetics and Genomics (ACMG) guideline states that treatment must be lifelong, with a goal of keeping blood phenylalanine in the range of 120–360 µmol/L.[ACMG] source: ACMG guideline: Vockley et al., Genet Med 2014 (PubMed 24385074) (opens in a new tab)

The guideline notes that the field moved toward “treatment for life” in part because neurodevelopmental and psychological problems have been seen even in people treated from birth, and because elevated maternal Phe is toxic to fetal development.[ACMG] source: ACMG guideline: Vockley et al., Genet Med 2014 (PubMed 24385074) (opens in a new tab) Ask your clinic how to read your own results.

Standard treatment for PKU is a diet low in Phe, and a low-protein diet is recommended for life.[NPKUA] source: National PKU Alliance: About PKU (opens in a new tab) Milk, eggs, and many other common foods contain large amounts of phenylalanine, and the artificial sweetener aspartame also contains phenylalanine.[MedlinePlus] source: MedlinePlus Medical Encyclopedia: Phenylketonuria (NIH) (opens in a new tab)

Because protein is restricted, people with PKU rely on special medical foods (formula) as a protein source that is extremely low in phenylalanine, taken every day for life.[MedlinePlus] source: MedlinePlus Medical Encyclopedia: Phenylketonuria (NIH) (opens in a new tab) Medical foods are considered an essential part of the standard of care.[NPKUA] source: National PKU Alliance: About PKU (opens in a new tab) Medication is an option for some people; the ACMG guideline describes pharmacotherapy as a developing area of treatment.[ACMG] source: ACMG guideline: Vockley et al., Genet Med 2014 (PubMed 24385074) (opens in a new tab) Ask your clinic which options may fit you.[NPKUA] source: National PKU Alliance: Treatment options (opens in a new tab)