AMINO ACID DISORDER
Disorder name: This is a group of birth defects found in some babies born to mothers who have PKU. Women with PKU who are not treated before or during pregnancy have a high risk of having babies with one or more of these health problems. Maternal PKU symptoms may include microcephaly (heads and brains that are very small), intellectual disability, heart defects, and low birth weight.
- What is PKU?
- What causes PKU?
- If PKU is not treated, what problems occur?
- What is the treatment for PKU?
- What happens when PKU is treated?
- What causes the PAH enzyme to be absent or not working correctly?
- How is PKU inherited?
- Is genetic testing available?
- What other testing is available?
- Can you test during a future pregnancy?
- Can other members of the family have PKU or be carriers?
- Can other family members be tested?
- How many people have PKU?
- Does PKU happen more often in a certain ethnic group?
- Does PKU go by any other names?
- Where can I find more information?
This fact sheet contains general information about PKU. Every child is different and some of these facts may not apply to your child specifically. Certain treatments may be advised for some children but not others. All children with PKU should be followed by a metabolic doctor in addition to their primary care provider.
If your newborn has had a ‘presumptive positive screen for PKU’ as a result of A screening test that looks for different disorders using a small sample of blood taken from a newborn’s heel. A positive or abnormal newborn screening result means that there are slight differences that were found in the baby’s blood, and further testing is needed to figure out if the baby has a metabolic disorder., it does not yet mean that he or she has PKU. There are other tests that need to be done to confirm whether your baby actually has PKU. Some babies are found not to have PKU and do not need treatment. Others are found to have a milder condition called “hyperphenylalaninemia” – also called ‘hyperphe’ or ‘non-PKU HPA.’ Many children with non-PKU HPA do not need treatment.
There is also another type of non-PKU HPA that is treated with a medication called BH4 (tetrahydrobiopterin). This condition is rare (less than 2% of cases). Blood and urine tests can be done to determine whether your child has this type of non-PKU hyperphe.
This fact sheet contains information about classic PKU only. Therefore, the details below are relevant only to babies who have been confirmed to have classic PKU. It does not contain information on non-PKU HPA or other A variant is a change or alteration in a person’s DNA sequence. Variants can happen in genes and affect how the gene functions. There are different types of variants – they can be non-problem causing (benign), disease-causing (pathogenic) or of unknown significance. The term variants is now used in place of the term mutation..
WHAT IS PKU?
PKU stands for “phenylketonuria.” It is one type of amino acid disorder. People with PKU have problems breaking down an amino acid called phenylalanine from the food they eat.
|Amino Acid Disorders:
These are a group of rare inherited conditions. People with amino acid disorders cannot digest particular amino acids – the building blocks of protein. These amino acids, along with other toxic substances, build up in the body. This can cause serious effects on health, growth, and learning. are a group of rare Acquiring a trait from one’s parents. Most traits, such as eye color or hair color, are inherited from a parent through genes. conditions. They are caused by A molecule that helps chemical reactions take place. For example, enzymes in the stomach speed up the process of breaking down food. Each enzyme can participate in many chemical reactions without changing or being used up. that do not work properly. A molecule that makes up many parts of every cell in the body. Examples of proteins include hormones, enzymes, hair, and antibodies. Proteins are made up of 20 different types of individual units called amino acids. It is the order of these amino acids in a protein that determines what form and function a protein has. Each gene holds the instructions for making a single protein. is made up of smaller building blocks called Amino acids are small molecules that make up proteins. There are over 100 different amino acids, but our body uses only 20 amino acids to make all of its proteins. Our genes determine the sequence of amino acids in a protein. This sequence determines what shape the protein takes, and what function that protein serves in the body.. A number of different enzymes are needed to process these amino acids for use by the body. Because of missing or non-working enzymes, people with amino acid disorders cannot process certain amino acids. These amino acids, along with other toxic substances, then build up in the body and cause problems.The symptoms and treatment vary between different amino acid disorders. They can also vary from person to person with the same amino acid disorder. See the fact sheets for each specific amino acid disorder.Amino acid disorders are inherited in an autosomal recessive manner and affect both males and females.
WHAT CAUSES PKU?
In order for the body to use protein from the food we eat, it is broken down into smaller parts called amino acids. Special enzymes then make changes to the amino acids so the body can use them.
PKU occurs when an enzyme, called “This is one of 20 amino acids that make up protein. It is also called “Phe.” It is not made by the body and must be eaten in the diet. It is found in all foods that contain protein. hydroxylase” (PAH), is either missing or not working properly. The job of this enzyme is to chemically change the amino acid phenylalanine (Phe – pronounced ‘fee’) into other substances. When a child with PKU eats food containing Phe, it builds up in the blood and causes problems. Phe is found in almost every food, except pure fat and sugar.
IF PKU IS NOT TREATED, WHAT PROBLEMS OCCUR?
Babies with PKU seem perfectly normal at birth. The first symptoms are usually seen around 6 months of age. Untreated infants may be late in learning to sit, crawl and stand. They may pay less attention to things around them. Without treatment, a child with PKU will have intellectual disabilities.
Some of the effects of untreated PKU include:
- intellectual disabilities
- behavior problems
- This refers to children who are unusually overactive. These children have serious problems sitting still. They tend to fidget and run around much more than usual. Some children with hyperactivity need treatment. They may be helped by behavior treatment, medication or both of these therapies.
- restlessness or irritability
- These are also called "convulsions" or "fits." During a seizure, a person loses consciousness and control of his or her muscles. It may also cause involuntary movements. Seizures can happen for many reasons. Some causes are metabolic disorders, a metabolic crisis, brain injury, and infection.
- a skin condition called This is a skin condition that causes an itchy red rash. It also leads to rough, scaly skin or blisters. It is usually located on the face, elbows, knees and arms. Two of the many causes are allergies or certain inherited metabolic disorders.
- a “musty” or “mousy” body odor
- fair hair and skin
WHAT IS THE TREATMENT FOR PKU?
Your baby’s primary doctor will work with a metabolic doctor and a dietician experienced with PKU to care for your child.
Prompt treatment is needed to prevent intellectual disabilities. Newborns need to drink a special medical formula. It is still possible to breastfeed your baby as long as you get help from your This is a person with special training in food and nutrition. A registered dietician (RD) has met the necessary educational requirements and has passed a national examination. If your child has a metabolic disorder, it is important for you to work with a registered dietician. They help create healthy food plans for people with metabolic disorders or other special needs.. Babies who are breastfed usually need the medical formula as well.
Most children need to eat a special diet made up of very low-protein foods, special medical foods, and the special formula. You must start the low-Phe diet as soon as you know your child has PKU. Your dietician will create a food plan that contains the right amount of protein, nutrients, and energy to keep your child healthy. The diet should be continued throughout life.
The following are treatments often advised for children with PKU:
1. Medical formula
Even though they need less Phe, children with PKU still need a certain amount of protein. The medical formula gives babies and children with PKU the nutrients and protein they need while helping keep their Phe levels within a safe range.
Your This is a doctor or medical geneticist who has special training in diagnosing and treating metabolic disorders. They often work in university hospitals or large medical centers. and dietician will tell you what type of formula is best and how much to use. Some states offer help with payment and some require private insurance coverage for the formula and other special medical foods.
2. Low-Phe food plan
The low-Phe food plan is made up of foods that are very low in Phe which is found in protein. This means your child must avoid or strictly limit foods that are high in protein including the following foods:
- milk and all dairy products including cheese, yogurt, ice cream
- regular formula
- meat and poultry
- nuts and peanut butter
- dried beans
- regular flour
It is very important that your child avoid the sugar substitute aspartame (sold under the brand names “Equal”, Nutrasweet” “Sweetmate”, “Canderal”). This is one type of sugar substitute. It is made up of the amino acids phenylalanine (Phe) and aspartic acid (Asp). It is sold under the brand names “Equal,” “Nutrasweet,” “Sweetmate” and “Canderal.” Aspartame is harmful for people with PKU because it causes Phe to build up in the blood. High levels of Phe can cause health problems and brain damage. It is important for people with PKU to avoid any foods or drinks that contain aspartame. contains high amounts of Phe. It can quickly raise the blood levels of Phe in people with PKU. Your child must not have any diet foods or drinks that contain aspartame. Some medicines and vitamins also contain aspartame. If you’re not sure, ask your pharmacist, metabolic doctor or dietician.
Many vegetables and fruits have only small amounts of Phe and can be eaten in carefully measured amounts. In addition, there are other medical foods such as low-Phe flours, baking mixes, breads, and pastas that are made especially for people with PKU.
Your child’s food plan will depend on many things such as his or her age, weight, general health, and blood test results. Your dietician will fine-tune your child’s diet over time.
Your child should follow this diet throughout life. Adults who do not stay on the diet and have high levels of Phe in their blood may notice some of the following:
- trouble paying attention
- problems making good decisions
- slow thinking
- bone loss (osteopenia)
Women need to be on the low-Phe diet before becoming pregnant. They need to stay on the diet throughout pregnancy. This will lessen the chance for serious health and learning problems in their babies.
3. The process of testing a disease for a person who does not appear to have the disease (non-symptomatic or asymptomatic). The goal of tracking is to find the disease in its earliest stages. Phe levels
Babies and young children with PKU need to have regular blood tests to measure their Phe levels. If there is too much or too little Phe in the blood, the diet and formula may need to be adjusted.
4. Enzyme cofactors
Cofactors are proteins that help an enzyme function. BH4 (tetrahydrobiopterin) is a substance made by the body. Kuvan® (sapropterin dihydrochloride) is a synthetic form of this substance. Both work to help the PAH enzyme change Phe into Tyr.
Some children with PKU will benefit from taking enzyme cofactors in pill form. This treatment is helpful in reducing blood Phe levels in some children with PKU. About 10% of children with classic PKU respond to enzyme cofactors. Most children with mild PKU are helped by enzyme cofactors.
Your doctor can do blood tests to determine whether your child responds to enzyme cofactors. Do not take enzyme cofactors unless advised by your metabolic doctor.
5. Pregnancy in women with PKU (“Having to do with the mother. PKU”)
Women with PKU who are not on the low-Phe diet when they become pregnant have a high chance of having babies with birth defects and intellectual disabilities.
Women who are not on the diet usually have high levels of Phe in their blood. The extra Phe gets to the fetus and causes problems with brain and body growth. Babies of untreated mothers may have the following:
- small brains
- intellectual disabilities
- birth defects of the heart
- low birth weight
This condition is called “This is a group of birth defects found in some babies born to women who have PKU. Women with PKU who are not treated before and throughout pregnancy have a high chance to have babies with one or more of these health problems. Symptoms of maternal PKU can include microcephaly (heads and brains that are too small), intellectual disabilities, heart defects, and low birth weight.”.
Women with PKU who want to have children need to have very low blood Phe levels before they get pregnant. During pregnancy, they need to:
- stay on the low-Phe diet
- visit their PKU clinic on a regular basis
- have their blood Phe levels checked often
WHAT HAPPENS WHEN PKU IS TREATED?
Children with PKU who start treatment soon after birth and keep their Phe levels within the suggested range usually have normal growth and intelligence. Some children, even when treated, have problems with schoolwork and may need extra help.
If treatment is not started until several weeks after birth, delays or learning problems may occur. The level of delay varies from child to child.
Children who start treatment after 6 months of age often have intellectual disabilities. Treatment is still important, even if started late, because it can help control behavior and mood problems and can prevent further damage to the brain.
WHAT CAUSES THE PAH ENZYME TO BE ABSENT OR NOT WORKING CORRECTLY?
Genes tell the body to make certain enzymes. THE PAH gene instructs the body how to make the PAH enzyme. People with PKU have changes in both copies of their PAH A segment of DNA that contains the instructions to make a specific protein (or part of a protein). Genes are contained on chromosomes. Chromosomes, and the genes on those chromosomes, are passed on from parent to child. Errors in the DNA that make up a gene are called variants and can lead to diseases. which cause them to not work correctly. Because of the changes, also called variants, in the PAH genes, the PAH enzyme either does not work properly or is not made at all.
HOW IS PKU INHERITED?
PKU is inherited in an autosomal recessive manner. It affects both boys and girls equally.
Everyone has two copies of the PAH gene that makes the PAH enzyme. In children with PKU, neither of these genes works correctly. These children inherit one non-working PAH gene from each parent.
Parents of children with PKU rarely have the condition themselves. Instead, each parent has a single non-working PAH gene. They are called A person who has one copy of a gene mutation for a particular autosomal recessive disorder (remember genes come in pairs). Carriers are not affected by the disorder. However, they can pass on the gene variant to their children. Children who inherit two such gene variants will be affected by the disorder. The term variants is now used in place of the term mutation.. Carriers do not have PKU because their other PAH gene is working correctly.
When both parents are carriers, there is a 25% chance in each pregnancy for the child to have PKU. There is a 50% chance for the child to be a carrier, just like the parents. And, there is a 25% chance for the child to have two working genes.
Relating to (or due to) genes and heredity or the field of studying genes and heredity. counseling is available to families who have children with PKU. Genetic counselors can answer your questions about how PKU is inherited, choices during future pregnancies, and how to test other family members. Ask your doctor about a referral to a These are health care providers who have special training in genetic conditions. They help families understand genetic disorders and how they are passed down. Genetic counselors offer information and support to people who have genetic conditions in their families or are concerned that they may have a child with an inherited disorder..
IS GENETIC TESTING AVAILABLE?
Genetic testing for PKU is available. Genetic testing, also called DNA testing, looks for changes (variants) in the PAH genes that causes PKU.
Deoxyribonucleic acid (DNA) is a molecule found in the chromosomes that carries genetic information. DNA is composed of four units (called bases) that are designated A, T, G, and C. The sequence of the bases spell out instructions for making all of the proteins needed by an organism. A gene is a section of DNA that holds the instructions for a specific protein. A change in one or more of the DNA bases making up a gene is called a mutation. Some mutations change the protein instructions and can lead to particular health problems or disorders. Each parent passes half of their chromosomes, and thus half of their DNA instructions, onto their children. It is these instructions that cause certain traits, such as eye or hair color, to be inherited. testing is not necessary to diagnose your child. It is sometimes helpful to know the gene changes in a child with PKU because it may help the doctors and dietician develop the best treatment plan. It is sometimes of help in determining which children will respond to biopterin supplements. It can also be helpful for carrier or prenatal testing, discussed below.
WHAT OTHER TESTING IS AVAILABLE?
PKU is confirmed by measuring the amount of Phe and Tyr in a blood sample. Talk to your doctor or your genetic counselor if you have questions about testing for PKU.
CAN YOU TEST DURING A FUTURE PREGNANCY?
If both gene changes (variants) have been found in your child with PKU, DNA testing can be done during future pregnancies. The sample needed for this test is obtained by either CVS or This is a test done during pregnancy. A needle is used to remove a small sample of fluid from the sac around the fetus. The sample can be used to test for certain genetic disorders in the fetus. Amniocentesis to test for genetic conditions is usually done between 13 and 20 weeks of pregnancy..
Parents may choose to have testing during pregnancy or wait until birth to have the baby tested. Parents may also choose to use assisted reproductive techniques to decrease the chance that their future children would have PKU. A genetic counselor can talk to you about your choices and answer questions about prenatal testing or testing your baby after birth.
CAN OTHER MEMBERS OF THE FAMILY HAVE PKU OR BE CARRIERS?
If they are healthy and developing normally, older brothers and sisters of a baby with PKU are unlikely to have PKU. Talk to your doctor or genetic counselor if you have questions about your other children.
Brothers and sisters who do not have PKU still have a chance to be carriers like their parents. Except in special cases, carrier testing should only be done in people over 18 years of age.
If you are a parent of a child with PKU, your brothers and sisters have a 50% chance to be a carrier. It is important for other family members to be told that they could be carriers. There is a small chance they are also at risk to have children with PKU.
All states offer newborn The process of testing for disease in a person who does not show signs of having the disease (nonsymptomatic or asymptomatic person). The goal of screening is to catch the disease in its early stages. for PKU. However, when both parents are carriers, newborn screening results are not sufficient to rule out the condition in a newborn baby. In this case, special diagnostic testing should be done in addition to newborn screening. It is very important that this testing be done immediately – ideally at 24 hours of age.
CAN OTHER FAMILY MEMBERS BE TESTED?
If there is concern about whether they have the condition, your other children can be tested to see if they also have PKU. Talk to your doctor or genetic counselor if you have questions about testing for PKU.
If both gene changes in the PAH gene have been found in your child, other family members can have DNA testing to see if they are carriers. If DNA testing is not helpful, other methods of carrier testing may be available. If you have questions about carrier testing, ask your genetic counselor or metabolic doctor.
HOW MANY PEOPLE HAVE PKU?
About one in every 10,000 Caucasian babies in the United States is born with PKU.
DOES PKU HAPPEN MORE OFTEN IN A CERTAIN ETHNIC GROUP?
PKU happens in people of all ethnic groups around the world. It happens more often in people whose families come from Ireland and other parts of Northern Europe. It is also more common in people from Turkey and those who are Native Americans. PKU is less common in people of African, Japanese or Ashkenazi Jewish backgrounds.
About 1 in every 50 Caucasians is a PKU carrier.
DOES PKU GO BY ANY OTHER NAMES?
PKU is sometimes also called:
- hyperphenylalaninemia – classic type
- phenylalanine hydroxylase deficiency
- PAH deficiency
Some variants of hyperphenylalaniemia not discussed in this fact sheet are:
- hyperphenylalanemia – mild type (non PKU-HPA)
- biopterin deficiency
- dihydropteridine reductase (DHPR) deficiency
- Guanosine triphosphate cyclohydrolase (GTPCH) deficiency
- 6-pyruvoyl tetrahydrobiopterin synthase (PTPS) deficiency
- Pterin-4 acarbinolamine dehydratase (PCD) deficiency
WHERE CAN I FIND MORE INFORMATION?
National PKU Alliance
Metabolic Support UK
Baby’s First Test
|Reviewed by:||HI, CA, OR, and WA metabolic specialists|
|Review date:||October 5, 2010
November 14, 2012
March 9, 2020
March 1, 2023
|Update on:||March 1, 2023|
THIS INFORMATION DOES NOT PROVIDE MEDICAL ADVICE. All content (“Content”), including text, graphics, images and information are for general informational purposes only. You are encouraged to confer with your doctor or other health care professional with regard to information contained on this information sheet. After reading this information sheet, you are encouraged to review the information carefully with your doctor or other healthcare provider. The Content is not intended to be a substitute for professional medical advice, diagnosis or treatment. NEVER DISREGARD PROFESSIONAL MEDICAL ADVICE, OR DELAY IN SEEKING IT, BECAUSE OF SOMETHING YOU HAVE READ ON THIS INFORMATION SHEET. This project is supported by a grant from the Maternal and Child Health Bureau, Health Resources and Service Administration, Genetic Services Branch, MCH Project #:UH7MC30774-01-00http://mchb.hrsa.gov