General Condition Information
- Benign hyperphenylalaninemia
- Benign hyperphenylalaninemia (due to phenylalanine hydroxylase deficiency, GTP cyclohydrolase I deficiency, pterin-4-alpha carbinolamine dehydratase deficiency, and 6-pyruboyltetahydropterin synthase deficiency)
- Benign hyperphenylalaninemia defect
- The prevalence of this condition is currently unknown. It is a very rare condition.
What is Non-PKU hyperphenylalaninemia
Non-PKU hyperphenylalaninemia, also called variant phenylketonuria, is an inherited (genetic) condition that prevents the body from processing proteins correctly. Your body breaks down the protein that you eat into parts called amino acids. Your body then uses those amino acids to make other proteins that it needs to function.
There are different forms of hyperphenylalaninemia (also called phenylketonuria). All the forms result in high levels of an amino acid called phenylalanine in the body.
In hyperphenylalaninemia, an enzyme called phenylalanine hydroxylase (PAH) is not made correctly. This enzyme helps change phenylalanine into other amino acids that your body needs.
When PAH is missing or severely damaged, phenylalanine cannot be processed. This more severe version of hyperphenylalaninemia is called classic phenylketonuria or PKU. When the enzyme PAH is made incorrectly but can still process some phenylalanine, this version is called non-PKU hyperphenylalaninemia. Non-PKU hyperphenylalaninemia has milder signs and symptoms compared to classic PKU.
Newborn Screening and Follow-Up
Newborn screening for non-PKU hyperphenylalaninemia is done using a small amount of blood collected from your baby’s heel. To learn more about this process, visit the Blood Spot Screening page.
During screening, a special machine measures how much phenylalanine is in your baby’s blood. Babies with high levels of phenylalanine might have non-PKU hyperphenylalaninemia.
If your baby’s blood spot screening result for non-PKU hyperphenylalaninemia is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.
An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. To learn more about screening results, visit the Blood Spot Screening Results page.
Your baby may need the following tests after an out-of-range screening result:
- Blood and/or urine tests
- Genetic testing using a blood sample
You should complete any recommended follow-up testing as soon as possible.
False-positive newborn screening results for this condition are rare. However, some situations can affect screening results:
Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions.
Because non-PKU hyperphenylalaninemia is a mild form of classic phenylketonuria (PKU), babies with non-PKU hyperphenylalaninemia do not usually show signs or symptoms. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.
The condition is caused by a change in the PAH gene. This gene gives your body instructions for making the enzyme phenylalanine hydroxylase. This enzyme helps break down the amino acid phenylalanine.
Without a working PAH gene, your baby’s phenylalanine hydroxylase enzyme doesn’t work as well. If phenylalanine is not broken down, it can build up to harmful levels. Babies with non-PKU hyperphenylalaninemia break down some phenylalanine, but not as much as babies without this condition. Usually, enough phenylalanine is broken down that it is not harmful to the baby.
- Non-PKU hyperphenylalaninemia is an autosomal recessive condition. Babies inherit it when each parent passes down a nonworking PAH gene to their baby. Only babies with two nonworking PAH genes—one from the mom and one from the dad—have this condition.
- People with one working copy and one nonworking copy of the PAH gene are called carriers.
- Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
- If two parents are carriers of a nonworking copy of the PAH gene, they have a 1 in 4 chance of having a child with non-PKU hyperphenylalaninemia.
- Carriers for non-PKU hyperphenylalaninemia often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with non-PKU hyperphenylalaninemia.
- Parents who already have a child with non-PKU hyperphenylalaninemia still have a 1 in 4 chance of having another child with non-PKU hyperphenylalaninemia. This 1 in 4 chance stays the same for future children.
- Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it. Visit the National Society of Genetic Counselors to find a genetic counselor and the American College of Medical Genetics and Genomics to find a medical geneticist.
Treatment and Management
Most babies with non-PKU hyperphenylalaninemia do not require any treatment.
Some individuals with more severe forms of non-PKU hyperphenylalaninemia might need treatment. The goal of treatment is to prevent the health problems caused by this condition. It is important to talk to your health care provider about which treatment(s) are best for your baby. Treatments may include the following:
- Restricted diet low in foods that contain phenylalanine
- Special phenylalanine-free formula
- Medications that contain a substance called BH4 that helps the body process phenylalanine
Children with non-PKU hyperphenylalaninemia have healthy growth and development.