Phenylketonuria

Teenagers with phenylketonuria (PKU) are not known to have any health problems that cause differences or delays in puberty.

Most people with phenylketonuria (PKU) are diagnosed at birth following routine newborn screening. Because a diagnosis can be made so early in life, most people with PKU can be effectively treated and the most severe complications of the disorder will be avoided. Most people live normal lives without any change in life expectancy due to PKU, although they will have to follow a special diet and supplement that diet with certain medical foods. If an infant or child is not diagnosed promptly and treated early, they can experience severe, irreversible brain damage. In these instances, these people even as adults may need supervised care.

Phenylketonuria (PKU) is a genetic condition and there is no cure. A person will never outgrow the disorder. Years ago, doctors thought the people with PKU could go off their low-phenylalanine diet when they got older. However, doctors now strongly advise that people with PKU remain on a special diet for their entire lives.

People with phenylketonuria (PKU) must follow a special, low-protein diet for their entire lives. This is because a certain building block of protein, called phenylalanine, cannot be broken down in the bodies of people with PKU. For this reason, it is important to avoid phenylalanine in the diet for a person’s entire life if they have this condition. People with PKU must also eat special medical foods to help make up for nutrients that they miss getting because of their special diet. Current guidelines strongly recommend that people with PKU follow a special diet including using supplemental medical foods for their entire lives.

People with phenylketonuria (PKU) have trouble breaking down an amino acid, called phenylalanine. Because of this, PKU and similar disorders are sometimes classified as amino acid disorders. Amino acids are chemical ‘building blocks’ the body uses to produce certain proteins that are required for proper growth and development.

Some people with phenylketonuria (PKU) may choose to stop following their diet as they get older. This is called poor compliance. A low phenylalanine-diet, which is also a low-protein diet, is very restrictive and some people have trouble staying on the diet. Children, particularly older children, may stop following the diet because they are embarrassed or their classmates may make unkind comments. Children or teenagers who struggle with compliance should talk to their parents, physicians and a psychologist to work through these issues.

Sometimes people stop following the diet because it’s working well and they feel better. They may start to think that they do not need to follow the diet anymore or ‘cheat’ on the diet more and more often. However, the less they follow their diets, the more phenylalanine will keep building up in their bodies. PKU can cause problems before people realize it, and although they feel well overall, it can affect their school or work performance, social interactions and other aspects of life. The special diet to treat PKU must be followed for life. Even if someone feels better and their symptoms improve, they need to continue to follow their treatment plan as developed by their physician and medical team in order to continue feeling better.

In a family with phenylketonuria, tests can be done to see whether other family members are carriers for the disorder. However, the specific gene changes in that family needs to be known. If known, all siblings and other at-risk relatives can be tested. Molecular genetic testing, which are tests that look for changes to genes, can be performed. Carriers for phenylketonuria are not at risk of developing symptoms. A genetic counselor or a physician with experience in phenylketonuria can provide advice about how a confirmed diagnosis can affect other family members.

Sometimes your doctor may be able to put you in contact with other people affected with phenylketonuria. Support groups can put you in contact with other people or families that have phenylketonuria. Support groups for phenylketonuria include:

Georgia PKU Connect is dedicated to Georgia’s Phenylketonuria (PKU) community with a mission to connect PKU families and individuals with the support and resources they need to manage PKU and live healthy, productive lives.

Taking care of someone with a long-term or chronic condition can be tiring and challenging and this is no different for parents or other caregivers of people with phenylketonuria. If you are a caregiver in need of support, try to take time for yourself, set aside time for personal counseling, or look for other resources at http://caregiveraction.org/.

Dr. Robert Guthrie developed the first newborn screening test for phenylketonuria which became widely used in the 1960’s. The methods he devised for collecting and transporting blood samples on filter paper proved to be easy and cost effective. In honor of Dr. Guthrie newborn blood samples are collected on Guthrie cards.

People with phenylketonuria (PKU) will have to avoid many protein-rich foods, such as milk, eggs, cheese, soybeans, yogurt, nuts, chicken and red meat. These foods are high in phenylalanine. Other foods can be eaten, but only in a limited amount. This includes fruits, vegetables, and some cereals, rice, breads, and pastas.

All 50 states in the U.S. screen for phenylketonuria (PKU) at birth. PKU is one of the few disorders that it is mandatory for all states to screen for.

Phenylketonuria, or PKU, is a rare genetic disorder. People with this disorder lack a substance in the body called phenylalanine hydroxylase (PAH). This substance is an enzyme needed to break down an amino acid called phenylalanine. Phenylalanine is a ‘building block’ that we get from our food that is required for proper growth and development. Because people with PKU lack the enzyme PAH, the amino acid, phenylalanine builds up in the blood, brain and other tissues of the body. When phenylalanine builds up, it can damage the body and harm the brain. If untreated, PKU can eventually cause serious problems including intellectual disabilities, seizures, and behavioral problems. The main form of the disorder, classic PKU, is usually identified through newborn screening so treatment is often started before symptoms begin. People get phenylalanine mostly through what they eat. Phenylalanine is found in all foods containing protein and in some artificial sweeteners. PKU is treated by a low-protein diet and the use of Medical Foods (including specialized formulas) that contain very little or no phenylalanine. PKU is caused by changes (alterations) in the PAH gene and is passed on in a family in an autosomal recessive manner. There is a mild form called non-PKU hyperphenylalaninemia. These people have a mild buildup of phenylalanine in the body, but often do not require treatment.

Phenylketonuria (PKU) is an inherited disorder that increases the levels of phenylalanine in the blood. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. If PKU is not treated phenylalanine can build up to harmful levels in the body. The signs and symptoms of PKU vary from mild to severe. The most severe form of this disorder is known as classic PKU. Without treatment these children develop permanent intellectual disability. Light skin and hair, seizures, delayed development, behavioral problems and psychiatric disorders are also common. Less severe forms of this condition sometimes called variant PKU and non-PKU hyperphenylalaninemia have a smaller risk of brain damage. Babies born to mothers with PKU and women who no longer follow a low-phenylalanine diet have a risk of intellectual disability and other serious complications because they are exposed to very high levels of phenylalanine before birth. PKU is caused by changes (mutations) in the PAH gene. It is inherited in an autosomal recessive manner. Because PKU can be detected by a simple blood test and is treatable newborn screening is available for this disorder. The best treatment for PKU is low-protein diet and medical foods (including specialized formulas) for life.

Gene therapy is a type of treatment where doctors try and replace the defective gene in a person with an unaffected one that can produce the necessary enzyme. In phenylketonuria (PKU), doctors would replace the altered PAH gene with one that produces the enzyme phenylalanine hydroxylase. The U.S. Food and Drug Administration (FDA) has never approved a gene therapy treatment. Several are currently being studied in clinical trials. The National PKU Alliance has information on gene therapy studies for PKU.

If you miss a dose of PALYNZIQ for treating PKU, take the next dose as scheduled and to not take two doses of PALYNZIQ to make up for the missed dose.

Phenylketonuria is caused by gene changes in the PAH gene. People have about 20,000-25,000 genes in their bodies. Our genes contain our body’s genetic information, called DNA; genes are segments of DNA found on chromosomes. Genes are inherited from our parents and passed on to our children. Genes are like our body’s instruction manual – they control the growth, development and normal function of the body. Genes produce specific proteins that the body needs to grow and work properly. When there is an unexpected change in a gene, the protein that the gene produces may be absent or not work properly.

A baseline blood phenylalanine concentration is required before initiating treatment.
The recommended initial dosage is 2.5 mg subcutaneously once weekly for 4 weeks. PALYNZIQ dose should be titrated in a step-wise manner over at least 5 weeks based on tolerability to achieve a dosage of 20 mg subcutaneously once daily. Your PKU specialist will help to check and explain your tolerance to PALYNZIQ.

Blood phenylalanine monitoring

Obtain blood phenylalanine concentrations every 4 weeks until a maintenance dosage is established.
After a maintenance dosage is established, periodically monitor blood phenylalanine concentrations.
Patients will be counseled to monitor dietary protein and phenylalanine intake, and adjust as directed by their healthcare provider.

People have about 20,000-25,000 genes in their bodies. Phenylketonuria is caused by an unexpected change, called a mutation, in a gene called PAH. Our genes contain our body’s genetic information, called DNA. Genes are like our body’s instruction manual – they control the growth, development and normal function of the body. When a mutation happens in a gene, the gene cannot work properly. While mutations are gene changes that are harmful to genes, other types of gene changes are not harmful. A “variant” is another word for a change in a gene. Sometimes these changes are not associated with causing a genetic disease or condition, and other times they are. Variants can be benign (not disease causing), pathogenic (disease causing), or of unknown significance (possibly disease causing). Looking at a person’s genetic testing report can be helpful to know what type of variant or genetic change someone has inherited for phenylketonuria.

If your baby receives a positive result for high levels of phenylalanine from newborn screening, it does not mean that your child definitely has phenylketonuria (PKU). Newborn screening can cause "false positives" and there are a few other disorders that can cause a positive newborn screening test for high phenylalanine levels. Further testing is needed to know for sure whether a child has phenylketonuria (PKU).

It is recommended that individuals with phenylketonuria be seen by a team of people from multiple medical disciplines including a pediatrician and other physicians, nutritionists, dieticians, genetic counselors, social workers, nurses, and psychologists.

If your child with phenylketonuria is exhibiting behavioral problems, signs of depression, or other signs of a mental illness, there are a few different resources that may be helpful for them. For behavioral problems, counseling or behavioral therapy may be useful. For depression or other mental illnesses, counseling by a psychologist or being treated by a psychiatrist may be helpful for them as well.

The main form of phenylketonuria (PKU) is known as classic or classical PKU. The majority of people with PKU have the classic form. Some people have a milder form called benign hyperphenylalaninemia or non-PKU hyperphenylalaninemia. These people often do not require treatment. Other people may not fit into ether of these two forms and doctors may say these people have variant PKU.

Infants with phenylketonuria (PKU) appear normal at birth. Since PKU is often diagnosed through newborn screening, treatment is usually begun before symptoms develop. With prompt diagnosis and treatment, the severe complications of PKU can be avoided.

A variety of problems can develop in infants and children who are not diagnosed promptly or who go untreated or in people who voluntarily stop treatment. These problems including delays in reaching developmental milestones (things like walking and talking at an appropriate age),intellectual disability, seizures, tremors, and behavioral and psychiatric issues. Some people may have a musky body odor and skin problems like eczema. They may have fairer skin and lighter-colored hair than the rest of their family. Symptoms in one person can be different from the symptoms in another person. One person may only have mild symptoms while another person has very serious symptoms.

People with phenylketonuria (PKU) should avoid aspartame. Aspartame is an artificial sweetener that contains phenylalanine. Aspartame is one of the more common artificial sweeteners in use today. It is sold under the brand names NutraSweet® and Equal®. Aspartame is made by joining together the amino acids aspartic acid and phenylalanine. This artificial sweetener is found in a variety of products including diet sodas, diet foods, and other products. There are actually federal regulations that require that any food that contains aspartame to vary the following warning: "Phenylketonurics: Contains phenylalanine." Aspartame is also found in some medications, particularly medications for children. Talk to your pharmacist or physician about what medications may contain aspartame and what alternatives there are for your child.

After initiating treatment with PALYNZIQ, blood phenylalanine levels should be obtained every 4 weeks until a maintenance dosage is established. After a maintenance dosage is established, periodic blood phenylalanine monitoring is recommended to assess blood phenylalanine control.
Patients should monitor their dietary protein and phenylalanine intake throughout treatment with PALYNZIQ and may be counseled on how to adjust their dietary intake, as needed, based on blood phenylalanine concentrations.

There is newborn testing for phenylketonuria (PKU). Newborns are tested for PKU as a part of the newborn screening program in every state of the United States. During routine newborn screening, a tiny sample of blood is taken from the heel of a newborn. This test called a heel prick or Guthrie test involves getting a few drops of blood from a pinprick in the newborn’s heel. The blood is run through a machine that can detect high levels of phenylalanine. Most infants with PKU are detected shortly after birth through routine newborn screening.

As of June of 2016, there is no enzyme replacement therapy (ERT) available for people with phenylketonuria.

As of June 2017, there are about 40 studies for phenylketonuria listed on [link url="ClinicalTrials.gov” target=”_blank”>ClinicalTrials.gov, a government website that provides regularly updated information about federally and privately supported clinical trials. This is not a complete list of current research. Current studies are looking at the outcomes of pregnancy in women with phenylketonuria, continuing to evaluate the drug Kuvan, how well adult PKU patients are doing, neurocognitive outcomes in mild hyperphenylketonuria, and several new medications that may have a role in treating this disorder.

Most infants with phenylketonuria (PKU) are diagnosed through routine newborn screening or NBS. NBS shows high levels of phenylalanine in the blood in patients with PKU. Other disorders can cause this finding too. Additional testing may be necessary to rule out those conditions. For example, tetrahydrobiopterin or BH4 is a coenzyme that breaks down phenylalanine. Coenzymes are substances that are necessary for reactions to occur in the body. If this coenzyme is missing or not working properly, it leads to high levels of phenylalanine in the body. Testing urine or testing red blood cells can reveal a defect in BH4.

Genetic testing can be used to confirm a diagnosis of phenylketonuria, but is often not necessary. Some physicians recommend these tests to help create the most effective treatment plan or allow other family members to have genetic testing done. These tests involve studying the PAH gene for changes that cause the disorder. This can include targeted mutation analysis, where specific, known changes in a gene are looked for; sequence analysis, where a part or sequence of DNA within a gene is examined; or deletion/duplication analysis, where missing or extra regions of DNA are looked for within a specific gene. Molecular genetic testing must be done at specialized laboratories.

Phenylketonuria (PKU) is treated with a special low-protein diet and the use of special medical food or formulas that are low in phenylalanine. People with PKU lack the enzyme phenylalanine hydroxylase. Enzymes are substances that help reactions occur in the body. This specific enzyme is required to break down phenylalanine in the body. In people with PKU, phenylalanine builds up in the body and becomes harmful, specifically to the brain where it is toxic. Some phenylalanine in the diet is necessary for proper growth and development.

Some patients with PKU have virtually no enzyme activity, while others have a little bit of enzyme activity. So the amount of phenylalanine in the diet that people with PKU can tolerate is different in one person compared to another. For everyone with PKU, the amount of phenylalanine in their diet must be carefully counted and limited. The most effective treatment for PKU is a life-long, low-protein diet that should be followed from infancy through adulthood. The diets are often so restrictive that people do not get enough protein to support normal health or growth. To ensure that they receive sufficient nutrition, people with PKU will also need special phenylalanine-free medical formulas or medical food to supplement the diet. People with PKU must follow their medical plans. For example, they should take 100% of the medical formula each day that has been recommended by their doctors. If people with PKU follow their special dietary plans, they can avoid the more serious complications associated with the disorder. It is recommended that treatment begin within the first weeks of life or as early as possible.

Some individuals with PKU can benefit from a drug called Kuvan (sapropterin hydrochloride) made by BioMarin. This drug is approved by the Food and Drug Administration (FDA) to treat certain people with PKU. This medication allows some people to eat food with more phenylalanine without risking symptoms or negative effects. The drug must be taken along with a low-protein diet. The drug does not work for everyone with PKU.

In May, 2018, the FDA approved Palynziq, and additionally, on March 28, 2018, the European Medicines Agency accepted BioMarin’s submission of a Marketing Authorization Application. Palynziq is the first enzyme therapy approved for adults living with PKU. This medication has the potential to alter the course of PKU management by limiting the need for a Phe-restricted diet.

Different people with Benign Hyperphenylalaninemia will have different symptoms and different severities of disease. This is called variable expression.

Non-PKU hyperphenylalaninemia, sometimes called benign hyperphenylalaninemia or mild hyperphenylalaninemia, is a mild form of phenylketonuria (PKU), a rare genetic disorder where the body has trouble breaking down a specific protein building block called phenylalanine. People with PKU usually need to limit the amount of phenylalanine in their diet and drink special medical formulas that are phenylalanine-free. There is some debate among physicians as to whether these people need to follow a low-protein diet. Some people with non-PKU hyperphenylalaninemia may need to follow this sort of treatment, but others may not have any symptoms or may have low enough levels of phenylalanine that they do not need to follow the dietary treatment. Women with non-PKU hyperphenylalaninemia should be counseled about the risk to a fetus that exists when phenylalanine levels are too high in the mother during pregnancy.

Non-PKU hyperphenylalaninemia, sometimes called benign hyperphenylalaninemia or mild hyperphenylalaninemia, is a mild form of phenylketonuria (PKU), a rare genetic disorder where the body has trouble breaking down a specific protein building block called phenylalanine. People with PKU usually need to limit the amount of phenylalanine in their diet and drink special medical formulas that are phenylalanine-free. There is some debate among physicians as to whether these people need to follow a low-protein diet. Some people with non-PKU hyperphenylalaninemia may need to follow this sort of treatment, but others may not have any symptoms or may have low enough levels of phenylalanine that they do not need to follow the dietary treatment. Women with non-PKU hyperphenylalaninemia should be counseled about the risk to a fetus that exists when phenylalanine levels are too high in the mother during pregnancy.

The National PKU Alliance launched the PKU Patient Registry on January 17, 2017. In the PKU Patient Registry, information will be entered by the patient and not by clinic staff. Hosted by NORD, the platform that being used is a natural history study platform approved by the FDA that will track information including demographics, education, diagnosis, treatment, diet, medical history, and mood. Most of the questions were created using common data elements taken from validated questionnaires such as the GRDR, PROMIS and others for food and diet. The PKU Patient Registry allows for the ability to conduct "lightning polls." These are quick questions that are posted to obtain a sample poll and report results back immediately in an effort to keep participants engaged. Participants will have on going access to information they have entered and researchers will have the opportunity to request access to de-identified data for use in PKU research.

When a woman is pregnant, it is possible to test the baby for certain conditions before the baby is born. This is called prenatal diagnosis. Some parents who have a family member with phenylketonuria (PKU) may choose to test for the disorder before birth. PKU is caused by an unexpected change, called a mutation, in a gene called PAH. People have about 20,000-25,000 genes in their bodies. Our genes contain our body’s genetic information, called DNA. Genes are inherited from our parents and passed on to our children. Genes are like our body’s instruction manual – they control the growth, development and normal function of the body. When there is an unexpected change in a gene, the gene may not work properly. It is like a section of the body’s instruction manual is not correct, and it can cause problems with the normal development and functioning of the body. When there is a mutation in the PAH gene, it can cause PKU.

If the specific PAH gene change that is causing PKU in the family is known, then prenatal testing can be performed. During the pregnancy, a test called chorionic villus sampling (CVS) can be performed to remove a sample of tissue from the placenta. Another test, called amniocentesis, involves taking a sample of the amniotic fluid that surrounds and protects a developing fetus. Only one of these tests needs to be performed. Genetic testing can then be performed on the cells from the placenta or the amniotic fluid to look for the PAH gene change.

Families considering prenatal testing should set up an appointment with a genetic counselor. A genetic counselor can explain the testing options and discuss reasons a family may or may not want to do prenatal diagnosis for PKU. A genetic counselor can also help to explain the test results.

Phenylketonuria (PKU) is a rare disorder. It affects people of Turkish, Irish, Northern European, and East Asian heritage more often than people of other ethnic groups.

People with phenylketonuria need to be on a low-phenylalanine (low protein) diet. However, this can be very different. Some people can tolerate more phenylalanine in their diets than other people. Some people may be able to take a medication called Kuvan, which allows them to eat some foods with phenylalanine. Everybody with PKU is different and an individual’s can be different in the amount of phenylalanine that is allowed.

Women can breastfeed an infant with phenylketonuria (PKU), along with feeding their baby the required amount of specialized PKU formula. Breast milk contains very low levels of phenylalanine (only 12 to 14 mg of Phe per ounce in one study), lower than most of the commercially available formula on the market (24 to 28 mg of Phe per ounce). It is important to work with a metabolic dietitian experienced with PKU closely if you would like to breastfeed your baby. To find a metabolic dietitian specializing in diets for people with metabolic conditions including PKU, visit the GMDI Find a Metabolic Dietitian webpage.

Even if more than one person in the same family has phenylketonuria and the same genetic changes that causes the condition, that does not necessarily mean that they will all have the same symptoms or severity of the condition. If one child strictly follows the special diet and another child does not, then the child who does not follow the diet is at risk for more severe symptoms. It is also possible that some children may be able to tolerate more phenylalanine in their diets than a sibling. Reports in medical journals talk about siblings with PKU who have the same genetic change in the PAH gene but have different clinical symptoms.

Phenylketonuria (PKU) is inherited in an autosomal recessive manner. In order to have PKU a person must have genetic changes (mutations) in both copies of the gene that causes this disorder PAH. A person who has PKU inherits one mutated gene for PKU from each parent. The parents of an individual with PKU are usually unaffected because they only carry one copy of the gene mutation.

It is very important for women with phenylketonuria (PKU) to work with a metabolic dietitian before and during pregnancy to have a low phenylalanine diet and still get the nutrients necessary for a healthy pregnancy. For women who can’t afford formula and metabolic foods, the National PKU Alliance has a Maternal PKU Emergency Program (MPKUEAP) to assist women with PKU who are currently pregnant and have no access to medical foods due to financial barriers. To learn more about the program and complete and application, visit the National PKU Alliance website MPKUEAP program.

If you are a carrier of phenylketonuria (PKU), your future children will each have a 25% (1 in 4) chance to have PKU if your partner is also a carrier. You partner can have testing to determine if they are a carrier for PKU. If you partner is not a carrier, none of your children will have the disorder. However, there is a 50% chance that for each pregnancy that your child will also be a carrier for PKU.

If you are a carrier for phenylketonuria (PKU) and your partner is not, your children would each have a 50% (1 in 2) chance to be a carrier of this condition just like yourself. If one of your children is a carrier and so is their partner and they have children, there is a 25% (1 in 4) chance for each pregnancy that the child will have PKU.

People who have a genetic change in one of their two copies of the PAH gene are carriers for phenylketonuria. Carriers do not develop symptoms of the disorder. They are at risk of passing phenylketonuria on to their children if they have a child with someone else who is also a carrier.

The cost of special medical food for phenylketonuria (PKU) can be different for one person or family when compared to another. There are many factors to consider. The supplier, the specific formula and medical foods, whether a person has insurance, whether the insurance plan will cover special medical foods, how much phenylalanine a person can handle in their diet, and other factors. For this reason, it is difficult to give an approximation about how much the use of medical food product would cost any given person. The cost is much more than it would be feed someone without PKU, and can be very expensive for an average family. The National PKU Alliance estimates the average cost at approximately $7,000 per year for a family.

In the last few sessions of Congress, a bill has been introduced call the Medical Foods Equity Act. It has not been passed. This bill would require all federal programs to cover the cost of medical foods (formula and foods modified to be low in protein) for children and adults with PKU and similar disorders that require a special diet and supplemental medical foods.

Contact PKU support groups to learn about how much the PKU diet and supplemental medical foods may cost your family. These groups may also have advice for dealing with insurance companies and the best places to find these products. PKU support groups include The National PKU Alliance; the Children’s PKU Network; Canadian PKU and Allied Disorders; and the National Society for Phenylketonuria.

Doctors strongly recommend that people with phenylketonuria (PKU) remain on a special diet for life. There was a time where doctors believe that teenagers and adults could stop following the diet as they got older. Doctors no longer recommend this. Doctors know understand that when people stop following the diet that they may experience problems, even if those problems aren’t obvious. Research shows that teenagers who stop following the diet do not do as well in school. Adults can develop psychiatric issues including depression, anxiety and phobias, and may process information slowly. Doctors know advocate that people with PKU follow their special diet for life, and that people who have given up on the diet start following again as soon as possible.

With prompt diagnosis and treatment, people with phenylketonuria can avoid the most severe symptoms associated with this disorder and experience normal development. Their life expectancy will most likely be no different from someone without the disorder.

Phenylketonuria is inherited in an autosomal recessive manner. This is one way a disorder or trait can be passed down through a family. Everyone has two copies of the PAH gene; one received from their father and one from their mother. Autosomal recessive inheritance means that a person receives a nonworking copy of the PAH gene from both parents. The parents have one working copy of the gene and one nonworking copy. They are carriers for phenylketonuria. Carriers do not develop symptoms of the disorder.

When two parents who are carriers have children, each child of theirs will have a 25% chance for being affected with this condition. In this case, both parents would have passes along a nonworking copy of the gene and the child will have the disorder. When two parents who are carriers have children, there is a 50% chance that one parent will pass on the gene change and the other won’t, meaning the child will be a carrier for the disorder. There is also a 25% chance that both parents will pass along a working copy of the gene and the child will not have the disorder and will not be a carrier.

Phenylketonuria is inherited in an autosomal recessive manner. This is one way a disorder or trait can be passed down through a family. Everyone has two copies of the PAH gene; one received from their father and one from their mother. Autosomal recessive inheritance means that a person receives a nonworking copy of the PAH gene from both parents. The parents have one working copy of the gene and one nonworking copy; they are carriers for phenylketonuria. Carriers do not develop symptoms of the disorder. When two parents who are carriers have children, each child of theirs will have a 25% chance for being affected with this condition.

The official medical abbreviation for phenylketonuria is PKU.

Phenylketonuria (PKU) is caused by changes in the PAH gene. This gene produces a substance called phenylalanine hydroxylase (PAH). This is an enzyme which breaks down an amino acid called phenylalanine. Amino acids are chemical ‘building blocks’ the body uses to produce certain proteins that are required for proper growth and development. In classic PKU, there is very little or no activity of the PAH enzyme. Without this enzyme, phenylalanine levels build up in the blood and other tissues. Phenylalanine is particularly damaging to brain tissue where it causes brain damage. People get phenylalanine from their diets, primarily from high protein foods, such as meat, fish, poultry, eggs, cheese, milk, nuts, and beans. Even breads, rice, pastas, vegetables, and fruits have some amount of protein and contain phenylalanine. With early recognition and prompt treatment in a form of a low-phenylalanine diet the serious complications of PKU can be avoided.

PALYNZIQ™ (pegvaliase-pqpz) Injection is the first FDA-approved enzyme substitution therapy designed to address the underlying cause of phenylketonuria (PKU), a rare and genetic brain-threatening condition marked by an inability to break down phenylalanine (Phe). PALYNZIQ™ is a once-daily self-administered therapy, clinically proven to reduce blood Phe levels in adults with PKU who have uncontrolled blood Phe levels on existing management.
Left untreated, high levels of Phe can become toxic to the brain and may lead to serious neurological and neuropsychiatric-related issues, impacting the way a person thinks, feels, and acts. PKU requires daily lifelong management and affects just 350 US newborns each year.

PALYNZIQ is a PEGylated phenylalanine ammonia lyase (PAL) enzyme that helps to break down phenylalanine into ammonia and trans-cinnamic acid. PALYNZIQ substitutes for the deficient phenylalanine hydroxylase (PAH) enzyme in PKU patients to reduce the concentration of phenylalanine in the blood.

People have about 20,000-25,000 genes in their bodies. Our genes contain our body’s genetic information, called DNA. Genes are inherited from our parents and passed on to our children. Genes are like our body’s instruction manual – they control the growth, development and normal function of the body. When there is an unexpected change in a gene, the gene may not work properly. It is like a section of the body’s instruction manual is not correct, and it can cause problems with the normal development and functioning of the body. When there are changes in the gene called PAH a person can be affected with Phenylketonuria (PKU).

People with PKU have a gene change in both of their copies of the PAH gene; one received from their mother and one from their father. Their parents are “carriers” for PKU. They have a gene change in only one copy of the PAH gene. Carriers of a condition usually don’t have medical problems from the gene change. If there is a history of phenylketonuria (PKU) in your family, you may be a carrier for the disorder.

If the specific PAH gene change that is causing PKU in a family is known, then carrier testing can be performed on any at-risk relatives. A doctor will perform tests that detect whether a person has the specific gene change in the PAH gene that runs in that family. Families considering carrier testing should set up an appointment with a genetic counselor. A genetic counselor can explain the testing options and discuss reasons a family may or may not want to do carrier testing for PKU. A genetic counselor can also help to explain the test results.

Support groups have information about supporting research into phenylketonuria and most accept donations toward research. Some groups focus specifically on supporting research. To donate money that could go to help research for these conditions, you can donate to the National PKU Alliance; the Children’s PKU Network; or the Canadian PKU and Allied Disorders.

Most people phenylketonuria (PKU) are diagnosed after a positive result from newborn screening. During routine newborn screening, a tiny sample of blood is taken from the heel of a newborn. This test called a heel prick or Guthrie test involves getting a few drops of blood from a pinprick in the newborn’s heel. The blood is run through a machine that can detect high levels of phenylalanine. Sometimes, newborn screening may miss an infant with PKU. An infant with PKU may have microcephaly, a condition in which the head is smaller than would be expect for the infant’s age. Older children who haven’t been treated may have a musty body odor, lighter skin and hair than other family members, eczema, intellectual disability, developmental delays, and behavioral problems. If you believe your child may have phenylketonuria, talk to your pediatrician or a genetic counselor about your concerns. They can help decide if testing for PKU is right for you, and can order this testing if necessary.

To learn about ongoing clinical research into phenylketonuria ask a physician who specializes in the disorder. Genetic counselors and medical geneticists are also excellence sources of information about ongoing clinical trials and can offer advice about the pros and cons about participating in such a trial.

Ongoing studies for phenylketonuria can also be found on [link url="clinicaltrials.gov” target=”_blank”>clinicaltrials.gov, a service of the U.S. National Institutes of Health. In Europe, the EU Clinical Trial Register performs a similar service.

Support groups also have information about ongoing clinical trials as well as information and advice about participating in clinical trials. Support groups for phenylketonuria include the National PKU Alliance, the Children’s PKU Network and the Canadian PKU and Allied Disorders.

There are PKU clinics around the U.S. and genetic clinics that can help people with PKU. The National PKU Alliance has a Find-A-Clinic search option on its website that allows you to search for clinics by state. To find a genetics clinic near you, visit the Clinic Services Search Engine at American College of Medical Genetics and Genomics.

Some people with phenylketonuria (PKU) find it challenging when it’s time to move (transition) from pediatric to adult health care services. One big change is leaving a doctor with whom you have a long-standing relationship, a doctor who is familiar with both your condition and you. It can feel like ‘starting over’ as you’ll begin to work with new doctors and a new medical team. Another challenge in moving to adult care is that young adults must take greater responsibility for their health. They must manage their disorder and manage their medications. They must bear greater responsibility for decisions concerning their health. Adolescents should be encouraged to make decisions about their care as early as possible to make this transition easier. Some hospitals have programs to help children with chronic disease transition to adult care services.

Phenylketonuria support groups may also provide information or support on how to move from pediatric care to adult care services and what to expect. The National PKU Alliance has a website to help teens and adults with PKU.

In the United States, phenylketonuria (PKU) is estimated to affect anywhere from about 1 in 10,000 to 19,000 newborns. Phenylketonuria is more common in certain geographic areas around the world than in others. In some ethnic groups or specific populations, it may occur more often, while in others it may be very rare. PKU affects both boys and girls.

There are PKU clinics around the U.S. and genetic clinics that can help people with PKU. The National PKU Alliance has a Find-A-Clinic search option on its website that allows you to search for clinics by state. To find a genetics clinic near you, visit the Clinic Services Search Engine at American College of Medical Genetics and Genomics.

PKU support groups may be able to help you find a doctor in your area that has experience in treating and managing PKU patients. Support groups for PKU include the National PKU Alliance works to improve the lives of families and individuals associated with PKU through research, support, education and advocacy, while ultimately seeking a cure. The Children’s PKU Network was founded in 1991 to address the special needs and concerns of individuals and families with PKU. Canadian PKU and Allied Disorders provides accurate news, information and support to families and professionals dealing with phenylketonuria and similar, rare, inherited metabolic disorders. The National Society for Phenylketonuria in the United Kingdom exists to help and support people with PKU, their families and carriers. It was formed in 1973.

Individuals with phenylketonuria (PKU) should be seen by doctors from multiple medical disciplines including a pediatrician and other physicians, nutritionists, dieticians, genetic counselors, social workers, nurses, and psychologists. Your pediatrician may need to contact a pediatric metabolic specialist. You can provide your doctor or pediatrician with education materials such as the information found at GeneReviews or practice guideline recommendations from the American College of Medical Genetics and Genomics.

Support groups can also provide physician education materials that you can share with your doctor. Support groups for PKU include the National PKU Alliance works to improve the lives of families and individuals associated with PKU through research, support, education and advocacy, while ultimately seeking a cure. The Children’s PKU Network was founded in 1991 to address the special needs and concerns of individuals and families with PKU. Canadian PKU and Allied Disorders provides accurate news, information and support to families and professionals dealing with phenylketonuria and similar, rare, inherited metabolic disorders. The National Society for Phenylketonuria in the United Kingdom exists to help and support people with PKU, their families and carriers. It was formed in 1973.

There are some specific genetic changes in the PAH gene that are associated with phenylketonuria (PKU), non-PKU hyperphenylalaninemia (benign hyperphenylalaninemia), or variant PKU, but other genetic changes have been found in people with different types of PKU that range in severity. Because of this, it is hard to know what form of the condition or what symptoms a person might have by just looking at their genetic changes. Some genetic changes might mean a person is more likely to respond to treatment with BH4 cofactor or the amount of phenylalanine they can tolerate in their diet. If you have a genetic testing result for the PAH gene and want to know more information about what those changes mean, talk to a genetic counselor. A consultation with a doctor experienced in diagnosing or treating PKU is recommended to understand how specific genetic changes in the PAH gene will affect a person.

With careful treatment and management of phenylalanine levels, people with phenylketonuria can have normal growth and development, including normal intelligence. If the disorder is not treated properly in infancy and childhood, then severe neurological problems can develop. This includes intellectual disability. There is also growing evidence that older children or adults who do not follow their recommended treatment (i.e. diet and medical foods) can develop problems. These issues include reduced attention span, a reduced or slow ability to process information and psychiatric issues like depression, anxiety or phobias. Some people who follow their treatment plan may also develop very mild symptoms.

Because most people with phenylketonuria have two genetic changes in their PAH genes in all of the cells of their body, they would have the same genetic testing results on blood, saliva, or other body tissue from a biopsy. However, most genetic tests for phenylketonuria are done on the blood.

Phenylketonuria (PKU) is caused by a change in the PAH gene. Because of this change, people with PKU lack an enzyme. This enzyme is necessary to break down an amino acid called phenylalanine. The symptoms of PKU are caused by abnormally high levels of phenylalanine in the body. Anything that causes phenylalanine levels to rise in the body can make PKU worse. Most phenylalanine comes through the diet, since it is present in all foods containing protein. However, other things can cause phenylalanine levels to go up. This includes an unrelated illness like ones with high fevers or stomach problems, surgery, and injuries like fractures. They are also certain medications that contain phenylalanine. If your child is ill or injured, you should continue to follow your established treatment plan. You can contact your doctor and PKU team to learn if you need to alter your child’s diet or treatment during the illness or injury time.

People with phenylketonuria (PKU) must continually have their blood monitored to measure the amount of phenylalanine. Different doctors and different hospital may do this differently and ow often this testing is done can vary as well. Most doctors recommend monitoring the blood every week or every two weeks. After the age of 12, every two weeks to one a month may be sufficient. A blood sample can be taken from the heel in infants and toddlers or from the fingertip in older children and adults. Parents can learn how to take a blood sample from their children. This may be difficult at first, but it eventually becomes routine.

Parents of children with PKU and people with the disorder should work with their PKU medical team so they can work out a system for monitoring blood phenylalanine levels. Parents should consider working with their children so it will easier one day for the children to take over their own monitoring.

Phenylketonuria (PKU) does not affect fertility. Both men and women with PKU can have children. PKU is an autosomal recessive disease and the risk of someone with this condition having a child with the disorder is extremely low. All children of a person with PKU will be a carrier for the disorder, which means that they will inherit an altered copy of the PAH gene from the affected parent.

Women who have PKU must take special precautions when planning a pregnancy. If a woman has high levels of phenylalanine in the blood and body, it can cause a miscarriage or other problems with the fetus. However, as long as women follow their recommended treatment plans and maintain proper phenylalanine levels, they can have successful pregnancies and healthy babies.

PALYNZIQ™ (pegvaliase-pqpz) Injection is the first FDA-approved enzyme substitution therapy designed to address the underlying cause of phenylketonuria (PKU), a rare and genetic brain-threatening condition marked by an inability to break down phenylalanine (Phe). PALYNZIQ™ is a once-daily self-administered therapy, clinically proven to reduce blood Phe levels in adults with PKU who have uncontrolled blood Phe levels on existing management.
PALYNZIQ can cause a severe allergic reaction (anaphylaxis) that may be life-threatening and can happen any time during treatment with PALYNZIQ. The drug is therefore available only through the PALYNZIQ REMS, a restricted distribution program. Prescribers must be certified in the PALYNZIQ REMS and comply with the REMS requirements to prescribe PALYNZIQ. Prescribers will educate patient on how to use the drug and to carry an epinephrine pen always. Pharmacies must be certified in the PALYNZIQ REMS to dispense PALYNZIQ
Pharmacies must verify that PALYNZIQ is only dispensed to patients with documentation of safe use conditions.

People with phenylketonuria (PKU) should be able to travel safely and enjoyably. They may to be prepared when traveling, particularly when traveling by air or internationally. If you are traveling and you or your child has PKU, you may want to bring a letter from your physician explaining the medical necessity of any food or formula you are bringing with you. You may also carry information about their condition when they travel in case there is a medical emergency. If you are traveling abroad, you may want to contact your medical team to see where appropriate food and formula can be obtained.

Support groups and other parents or families with PKU can offer advice and information and how to make traveling with PKU easier and safe. The National PKU Alliance has a PDF booklet called My PKU Binder with a section about travel.

Aside from the dietary adjustments, in general, there are no special modifications that a person with a child with phenylketonuria would need to make to their home.

People with non-PKU hyperphenylalaninemia, or benign hyperphenylalaninemia, may or may not have symptoms. People with this form of PKU have more enzyme activity than people with the classic form of PKU. They can tolerate more phenylalanine in their diets and some people may not require treatment. Anything that cause phenylalanine levels to rise in the body can make PKU worse. Most phenylalanine comes through the diet, especially in high protein foods. However, other things can cause phenylalanine levels to go up. This includes an unrelated illness like ones with high fevers or stomach problems, surgery, and injuries like fractures. They are also certain medications that contain phenylalanine. If your child is ill or injured, you should continue to follow your established treatment plan. You can contact your doctor and PKU team to learn if you need to alter your child’s diet or treatment during the illness or injury time.

Most people with phenylketonuria (PKU) are diagnosed through newborn screening. Treatment is begun before symptoms develop and most people can avoid severe complications. In children who are diagnosed late or are not treated, severe neurological problems can develop. How these children perform in school depends on many factors including the degree of intellectual disability and how severe a form of the disorder they may have.

All children with PKU (even if they do not have any complications from PKU) are eligible for a 504 plan. A 504 plan organizes any unique requests needed by a child to fully participate in school. This plan is important for making sure a student with PKU can maintain their diet in school while fully participating in school with the same access to educational opportunities as all children. For example, access to formula in the classroom, so they don’t have to leave and miss instruction.

An IEP is A 504 plan ensures that students with disabilities can fully participate in school and have access to the same educational opportunities as all children.

Schools must work with families to provide an appropriate meal for children with special dietary needs like children with PKU. However, how this is done may vary by state. Usually a 504 plan is enough to set up food accommodations if special education services are not needed, but sometimes, an IEP may need to be created as well even is special education services are not needed. An IEP is an individualized document that is created together by parents and the school to guide the education of a child with a disability or special needs.

Parents should talk to their child’s school system and learn what they need to do for their child.

Parents are encouraged to provide a school with a packet of information on PKU and to work with school officials including teachers, nurses, psychologists, the principal, and other professionals. The National PKU Alliance has a handbook called the PKU Binder that has lots of information on how to handle school when your child has PKU. The Binder includes sample letters for daycare personnel and teachers. They also provide materials specifically for teachers to educate them about PKU.

The U.S. Department of Education has information on individual education plans and on 504 plans.

Phenylketonuria is also known as:

Other disorders beside phenylketonuria can cause elevated levels of the amino acid phenylalanine in the body. This includes a temporary (transient) elevation of phenylalanine in some infants (called transient hyperphenylalaninemia) or tetrahydrobiopterin (BH4) deficiency, a rare genetic neurological disorder of infancy. Tetrahydrobiopterin is a coenzyme, which helps to enhance the action of other enzymes. Enzymes are necessary for chemical reactions to occur in the body. BH4 works with phenylalanine hydroxylase (the enzyme people with PKU are missing) to break down phenylalanine in the body. A deficiency of this coenzyme leads to abnormally high blood levels of the phenylalanine.

One of the unique features that people with phenylketonuria can have is a "mousy” or “musty” odor to the skin, hair, sweat and urine. This odor comes from excessive levels of phenylalanine in the body.

There are different on-line calculators that can help you keep track of your phenylalanine levels. The National PKU Alliance has partnered with the How Much Phe? application for members to use the tracking site for one year.

For a time, doctors said it was all right for people with classic phenylketonuria (PKU) to ease up on their dietary restrictions. Doctors no longer believe this is okay. They now say that people must follow a low-phenylalanine (low protein) diet for their entire lives. Doctors have learned that when people stop following their diet symptoms can develop. This includes psychiatric symptoms like anxiety, depression or phobias, or it may take them longer to process information and may make it harder to do well in school, affect job performance, and even make social interactions more difficult. In fact, some people who follow a special diet from birth can still develop these symptoms as they get older. The key to reducing such issues is regularly monitoring and adapting their diets under the supervision of a medical team that includes a nutritionist and/or dietician.

There are several support groups for people with phenylketonuria. The National PKU Alliance works to improve the lives of families and individuals associated with PKU through research, support, education and advocacy, while ultimately seeking a cure. The Children’s PKU Network was founded in 1991 to address the special needs and concerns of individuals and families with PKU. Canadian PKU and Allied Disorders provides accurate news, information and support to families and professionals dealing with phenylketonuria and similar, rare, inherited metabolic disorders. The National Society for Phenylketonuria in the United Kingdom exists to help and support people with PKU, their families and carriers. It was formed in 1973.

Some states even have their own state PKU support group. One example of a state level support group is Georgia PKU Connect which is dedicated to Georgia’s Phenylketonuria (PKU) community with a mission to connect PKU families and individuals with the support and resources they need to manage PKU and live healthy, productive lives.

There are no particular sports or other activities that people with phenylketonuria (PKU) should avoid. In fact, regular exercise is a recommended part of a healthy lifestyle. People with PKU need to follow their special diet and regularly have their blood phenylalanine levels monitored. Other than restricting the types of food that they can eat, PKU, if diagnosed early and treated properly, will not limit people in other ways.

People with phenylketonuria (PKU) who are promptly diagnosed and treated early will avoid the serious complications of the disorder. Having PKU will not prevent them from working any specific type of job or pursuing almost any career they want to try. Having said this, there are restrictions in 2016 about individuals with PKU serving in the United States military.

Other disorders beside phenylketonuria can cause elevated levels of the amino acid phenylalanine in the body. This includes a temporary (transient) elevation of phenylalanine in some infants (called transient hyperphenylalaninemia) or tetrahydrobiopterin (BH4) deficiency, a rare genetic neurological disorder of infancy. Tetrahydrobiopterin is a coenzyme, which helps to enhance the action of other enzymes. Enzymes are necessary for chemical reactions to occur in the body. BH4 works with phenylalanine hydroxylase (the enzyme people with PKU are missing) to break down phenylalanine in the body. A deficiency of this coenzyme leads to abnormally high blood levels of the phenylalanine.

Phenylketonuria (PKU) is treated with a special low-protein diet and the use of special medical food or formulas that are low in phenylalanine. The most effective treatment for PKU is a life-long, low-protein diet that should be followed from infancy through adulthood. To ensure that they receive sufficient nutrition, people with PKU will also need special phenylalanine-free medical formulas or medical food to supplement the diet.

There are two medications that are approved by the U.S. Food and Drug Administration (FDA) for the treatment of people with phenylketonuria (PKU). The first drug is called Kuvan. It is made by BioMarin Pharmaceutical. Kuvan lowers the levels of phenylalanine in some people with PKU. This drug does not work for everyone with PKU. It only works for people who have what doctors call "BH4 responsive PKU." BH4, also called tetrahydrobiopterin, is a cofactor; it is an enzyme that works with another enzyme to break down substances in the body.

BH4 works with phenylalanine hydroxylase (PAH) to break down the amino acid phenylalanine in the body. People with PKU produce low levels or virtually no PAH. Kuvan works by stimulating whatever PAH a person has to help break down phenylalanine. Kuvan works only in people who have some residual PAH enzyme activity. Kuvan must be used along with a phenylalanine-restricted diet.

There is a second drug also manufactured by BioMarin for the treatment of PKU. PALYNZIQ™ (pegvaliase-pqpz) Injection is the first FDA-approved enzyme substitution therapy designed to address the underlying cause of phenylketonuria (PKU), a rare and genetic brain-threatening condition marked by an inability to break down phenylalanine (Phe). PALYNZIQ™ is a once-daily self-administered therapy, clinically proven to reduce blood Phe levels in adults with PKU who have uncontrolled blood Phe levels on existing management.

PALYNZIQ is a PEGylated phenylalanine ammonia lyase (PAL) enzyme that helps to break down phenylalanine into ammonia and trans-cinnamic acid. PALYNZIQ substitutes for the deficient phenylalanine hydroxylase (PAH) enzyme in PKU patients to reduce the concentration of phenylalanine in the blood.

Women with phenylketonuria are able to become pregnant and to have healthy children. However, women with PKU who want to become pregnant must take precautions, specifically they must track and keep their phenylalanine levels down. If these levels are high, women are at risk for miscarriage. Babies born to women with high phenylalanine levels are at risk for growth deficiency and a low birth weight, a small head circumference (microcephaly), and intellectual disability. Women with PKU who are planning to become pregnant should discuss their plans with their PKU medical team in order to take the proper steps to ensure their phenylalanine levels remain low enough to be safe for their unborn child.