General Condition Information
- Benign hyperphenylalaninemia (due to biopterin defect in co-factor biosynthesis)
- Biopterin cofactor biosynthesis defect
- Biopterin defect of cofactor biosynthesis
- Defect of biopterin cofactor biosynthesis
- Defects of biopterin cofactor biosynthesis
- Tetrahydrobiopterin deficiency
- This condition is one type of a group of rare conditions known as tetrahydrobiopterin deficiencies. Fewer than 10 babies are born with tetrahydrobiopterin deficiencies each year in the United States.
What is Biopterin defect in cofactor biosynthesis
Biopterin defect in cofactor biosynthesis is an inherited (genetic) condition that increases levels of a substance called phenylalanine in the blood. Phenylalanine is one kind of amino acid, which are the building blocks of protein. Your body uses amino acids to make other proteins that it needs to function.
Cofactors are substances that help enzymes work. Tetrahydrobiopterin (BH4), which is a type of biopterin, is a cofactor that helps certain enzymes process phenylalanine and important brain chemicals. Your body needs to build and recycle BH4 correctly for these important enzymes to work. Biopterin defect in cofactor biosynthesis occurs when the body cannot build BH4.
Biopterin defect in cofactor biosynthesis is one of a group of conditions called tetrahydrobiopterin deficiencies. Another condition in this group is called Biopterin Defect in Cofactor Regeneration, which occurs when BH4 is not recycled correctly.
Two enzymes in your body help build BH4. In biopterin defect in cofactor biosynthesis, one of these two enzymes does not work well. Without working BH4, the enzymes that need this cofactor as a helper cannot do important jobs in the body.
Babies with biopterin defect in cofactor biosynthesis cannot break down all of the phenylalanine from the proteins they eat. As a result, phenylalanine builds up to harmful levels in their body. Their body also makes fewer important chemicals for their brain called neurotransmitters. This can cause the signs and symptoms of the condition.
Newborn Screening and Follow-Up
Newborn screening for biopterin defect in cofactor biosynthesis 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 of a substance called phenylalanine is in your baby’s blood. In most cases, babies with high levels of phenylalanine have a condition called classic phenylketonuria (PKU). But, in some rare cases, babies with high levels of phenylalanine are found to have biopterin defect in cofactor biosynthesis. Whether a baby has PKU or a biopterin defect will be determined during follow-up testing.
If your baby’s blood spot screening result for biopterin defect in cofactor biosynthesis 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. Babies with this condition can have serious health problems if they are not diagnosed and treated quickly.
False-positive newborn screening results for this condition are rare. However, babies who receive supplemental nutrition (also called total parenteral nutrition [TPN] or hyperalimentation) may have out-of-range 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. 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.
Babies with biopterin defect in cofactor biosynthesis often seem healthy at birth, but they may develop signs of the condition over time. Eating foods with high amounts of phenylalanine (protein-containing foods), illness, infection, or going a long time without eating can trigger signs of the condition.
Signs of the condition may include the following:
- Delays in development
- Weak muscle tone (hypotonia)
- Difficulty swallowing
- Problems with controlling body temperature
- Sleepiness (lethargy)
- Behavioral problems
Biopterin defect in cofactor biosynthesis is caused by changes in one of two genes, called GCH1 or PTS. These genes give the body instructions for making two enzymes that build BH4. These enzymes are called guanosine triphosphate cyclohydrolase I (GTPCH) and 6-pyruvoyl tetrahydropterin synthase (PTPS).
The body cannot build enough normal BH4 without working GCH1 or PTS genes. Without enough working BH4, the body cannot break down phenylalanine and the brain cannot function as it should.
- Biopterin defect in cofactor biosynthesis is an autosomal recessive condition. Babies inherit the condition when each parent passes down the same nonworking gene that causes biopterin defect in cofactor biosynthesis (GCH1 or PTS) to their baby. Only babies with two matching nonworking genes—for example, one nonworking GCH1 from the mom and one nonworking GCH1 from the dad—have this condition. Babies with two nonworking genes that do not match—for example, one nonworking GCH1 from the mom and one nonworking PTS from the dad—will not have this condition.
- People with one working copy and one nonworking copy of the GCH1 or PTS 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 GCH1 or PTS gene, they have a 1 in 4 chance of having a child with biopterin defect in cofactor biosynthesis.
- Carriers for biopterin defect in cofactor biosynthesis 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 biopterin defect in cofactor biosynthesis.
- Parents who already have a child with biopterin defect in cofactor biosynthesis still have a 1 in 4 chance of having another child with biopterin defect in cofactor biosynthesis. This 1 in 4 chance stays the same for all 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
It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.
Treatments may include the following:
- Restricted diet that avoids foods with phenylalanine
- Medical formula and foods
- BH4 supplements to reduce phenylalanine levels
- Medicine to help/increase neurotransmitter levels
Children who receive early and ongoing treatment for biopterin defect in cofactor biosynthesis can have healthy growth and development.