Also known as:
- tetrahydrobiopterin deficiency
- BH4 deficiency
- hyperphenylalaninemia caused by a defect in biopterin metabolism
- non-phenylketonuric hyperphenylalaninemia
- disorders of biopterin biosynthesis
- biopterin cofactor defects
- guanosine triphosphate cyclohydrolase 1 deficiency
- 6-pyruvoyl-tetrahydropterin synthase deficiency
Biopterin defect in cofactor biosynthesis (BIOPT-BS) is a condition that causes high amounts of phenylalanine and other harmful substances to build up in the body. It is considered an amino acid condition because people with BIOPT-BS are unable to process certain amino acids, small molecules that make up proteins. Detecting the condition early and beginning treatment can often prevent the severe outcomes of BIOPT-BS.
BIOPT-BS is only one form of tetrahydrobiopterin deficiency. You can also read about the causes and treatment for a different form of tetrahydrobiopterin deficiency known as biopterin defect in cofactor regeneration.
Your baby’s doctor may ask you if your baby is showing any of the signs of BIOPT-BS (see Early Signs below). If your baby has certain signs, your baby’s doctor may suggest starting immediate treatment.
If your baby’s newborn screening result for biopterin defect in cofactor biosynthesis (BIOPT-BS) was out of the normal range, your baby’s doctor or the state screening program will contact you to arrange for your baby to have additional testing. It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition. An out-of-range result may occur because the initial blood sample was too small or the test was performed too early. However, as a few babies do have the condition, it is very important that you go to your follow-up appointment for a confirmatory test. Because the harmful effects of untreated BIOPT-BS can occur soon after birth, follow-up testing must be completed as soon as possible to determine whether or not your baby has the condition.
Follow-up testing will involve checking your baby’s urine and blood samples for signs of BIOPT-BS. Harmful amounts of certain substances build up in the body when a child has an amino acid condition, so measuring the amounts of these substances in your baby’s body can help doctors determine whether your baby has a condition. High amounts of phenylalanine in the blood and abnormal pterins in the urine might indicate that your baby has BIOPT-BS. Your baby’s doctor may also test a blood sample to find out if your baby’s enzymes are working properly.
About Biopterin defect in cofactor biosynthesis
Babies with BIOPT-BS usually seem healthy at birth. Signs of BIOPT-BS may develop over time. These signs include:
- Developmental delays
- Seizures (known as epilepsy)
- Behavioral troubles
- Trouble regulating body temperature (your baby may get cold easily)
- Poor sucking during feeding
- Weak muscle tone (known as hypotonia)
- Sleeping longer or more often
Many of these signs may occur when your baby eats foods that his or her body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections.
If your baby shows any of these signs, be sure to contact your baby’s health care provider immediately.
Individuals with biopterin defect in cofactor biosynthesis have trouble breaking down certain amino acids, including phenylalanine. This results in high levels of phenylalanine in the blood. Phenylalanine is found in many proteins and in artificial sweeteners. Everyone has some phenylalanine in his or her blood, but high levels can be toxic. A dietician or nutritionist can help you plan a healthy diet for your child.
Supplements and Medications
Your baby’s health care provider may prescribe BH4 supplements. BH4 is a substance naturally made by the body, but babies with BIOPT-BS may not make enough. BH4 supplements can help reduce high phenylalanine levels. Your baby’s doctor will need to write a prescription for these supplements.
Some children with BIOPT-BS may benefit from medication that raises dopamine levels. Dopamine is a chemical in the brain that helps send signals and messages. Children with BIOPT-BS may not make enough dopamine naturally. Taking these medications may help promote healthy growth and development in children with BIOPT-BS. Talk to your baby’s doctor before starting any of these medications.
Children who receive early and on-going treatment for BIOPT-BS can have healthy growth and development. This is why newborn screening for BIOPT-BS is so important.
Children who receive treatment may still experience some of the signs mentioned in the Early Signs section, as well as developmental disabilities or intellectual disabilities.
Children who do not receive treatment for BIOPT-BS are at risk of severe intellectual disabilities and brain damage.
When we eat food, enzymes help break it down. Some enzymes break down proteins into their building blocks, called amino acids. Other enzymes break down these amino acids. Enzymes sometimes need help form substances called co-enzymes. Co-enzymes attach to enzymes to help them do their jobs. Biopterin is an important co-enzyme for breaking down amino acids, especially the amino acid phenylalanine.
BIOPT-BS occurs when the body cannot make its own BH4, the substance from which biopterin is made. Babies with BIOPT-BS either do not produce enough or produce non-working enzymes for making BH4.
BIOPT-BS affects either the GTP cyclohydrolase I enzyme or the 6-pyruvol tetrahydropterin synthetase enzyme. If either of these enzymes does not work, then the body cannot make BH4. Without BH4, the body cannot make biopterin. When the body does not have biopterin, it cannot break down many amino acids, including phenylalanine. This causes phenylalanine levels to rise in the blood. Everyone has some phenylalanine in his or her blood, but high levels can be toxic.
BIOPT-BS is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for BIOPT-BS, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with BIOPT-BS is rare, when both parents are carriers, they can have more than one child with the condition. Learn more about autosomal recessive inheritance.
Support for Biopterin defect in cofactor biosynthesis
At this time we have not located a condition-specific support group for BIOPT-BS. However, there are resources that will be helpful in answering your questions about this condition.
Genetic and Rare Diseases Information Center (GARD) is staffed by experienced information specialists to answer questions in English and Spanish from the general public, including patients and their families, health care professionals and biomedical researchers. It was established by the National Human Genome Research Institute and the Office of Rare Diseases Research.
Mums National Parent-to-Parent Network provides support to parents of children with health conditions by connecting them to other parents who have a child with the same or a similar condition.
Your baby’s doctor may also be familiar with support organizations in your area. Ask your baby’s health care provider for more information about accessing support in your community.
If you are part of an organization that provides support for individuals with BIOPT-BS, please contact us so that more families affected by this condition can learn about the services your organization provides.
Work with your baby’s doctor to determine the next steps for your baby’s care. Your baby’s physician may help you coordinate care with a doctor who specializes in metabolism, a dietician who can help plan your child’s specialized diet, and other medical resources in your community. Some children with BIOPT-BS have developmental delays. If you think that your baby is not meeting his or her developmental milestones, ask your baby’s doctor about the next steps in accessing a developmental evaluation and care.
Because BIOPT-BS is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for BIOPT-BS, and understand what this diagnosis means for other family members and future pregnancies. Speak with your baby’s doctor about getting a referral. The Clinic Services Search Engine offered by the National Coordinating Center for the Regional Genetic and Newborn Screening Service Collaboratives and the Find a Genetic Counselor tool on the National Society of Genetic Counselors (NSGC) website are two good resources for you or your baby's health care provider to use to identify local specialists.