Phenylketonuria: Genetic Disorder

Updated on May 13th, 2019

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    Phenylketonuria, which is commonly known as PKU, is a genetic disorder that increases the levels of phenylalanine hydroxylase in the blood, which if harmful levels are reached, can cause intellectual disability and other serious health problems. We want you to have as much information possible about this disorder.

    That’s why we put together this comprehensive phenylketonuria guide.

    What Is Phenylketonuria?

    Phenylketonuria is a genetic disorder that causes increased levels of an amino acid called phenylalanine hydroxylase in the blood.

    It’s caused when there’s a mutation in the gene that creates the enzyme needed to break down phenylalanine hydroxylase, keeping the amino acid at normal levels.

    While these increased levels are typically fine on their own, phenylalanine hydroxylase is found in a lot of proteins and aspartame, an artificial sweetener. So when people with phenylketonuria consume protein and/or aspartame, phenylalanine hydroxylase builds up in their body, which can eventually lead to serious health problems including:

    • Irreversible brain damage and intellectual disability
    • Neurological problems such as tremors and seizures
    • Behavioral, emotional, and social problems in older children and adults

    How Common Is PKU?

    Phenylketonuria is a rare genetic disorder. In the United States, it affects approximately one in every 10,000 to 15,000 newborns.

    Typically, the condition is caught shortly after birth because a phenylketonuria test is required to be completed on all newborns.

    PKU Severities

    There are different levels of phenylketonuria. The most severe form of the disorder is called Classic PKU. This occurs when the enzyme needed to break down phenylalanine hydroxylase in the bloodstream is severely reduced or missing completely.

    This could result in dangerously high levels and even, severe brain damage.

    Mild and moderate forms of phenylketonuria have less severe outcomes because the enzyme retains some function. This results in a decreased risk of brain damage and less severe phenylketonuria symptoms.

    Phenylketonuria Symptoms

    Newborns with PKU don’t typically have any phenylketonuria symptoms at all, which is why a phenylketonuria test is required at birth.

    However, if PKU isn’t diagnosed immediately, newborns usually develop symptoms within a few months.

    Common phenylketonuria symptoms include:

    • Skin rashes such as eczema
    • Neurological problems, which may involve seizures
    • Musty odor on the skin, breath, or in the urine, which is caused by too much phenylalanine hydroxylase in the body
    • Fair skin and blue eyes — phenylalanine hydroxylase can’t transform into melanin, which is the pigment responsible for skin and hair tone
    • Hyperactivity
    • Abnormally small head
    • Delayed development
    • Intellectual disability
    • Behavioral, emotional, and social problems
    • Psychiatric disorders

    These symptoms can be either mild or severe. Also, as with other disorders, the symptoms seen vary from person to person.

    What Is the Life Expectancy of a Person With PKU?

    PKU life expectancy is the same as any completely healthy person, as long as the disorder doesn’t cause any major health issues. To help prevent these, people with this disorder should follow a phenylketonuria diet.

    This keeps phenylalanine hydroxylase from building up in the bloodstream to dangerous levels.

    While untreated phenylketonuria can lead to severe health issues, including brain damage, the disorder itself doesn’t lower the person’s life expectancy. However, when pregnant mothers with phenylketonuria have high levels of phenylalanine hydroxylase in their bloodstream it can cause fetal birth defects or miscarriage.

    Because of this, it’s extremely important for expecting mothers with phenylketonuria to follow a strict phenylketonuria diet.

    What Causes Phenylketonuria?

    Phenylketonuria occurs when there’s a mutation in the PAH gene, which causes the enzyme to malfunction. In mild and moderate cases, the enzyme functions at least partially, but in severe cases, the enzyme is either not present or doesn’t work at all.

    In the majority of cases, PKU is present at birth because it’s a genetic disorder passed down from parents to infants. Severe phenylketonuria causes major health problems, which might include brain damage and seizures.

    So it’s not too surprising that PKU is sometimes seen in adults with dementia and Parkinson’s disease as well. In these cases, the disease is the cause of phenylketonuria, genetics doesn’t play a major role.

    Instead, rapidly progressing dementia or Parkinson’s disease alters the brain chemistry to a point that the enzyme responsible for breaking down phenylalanine hydroxylase stops functioning properly.

    Is PKU Dominant or Recessive?

    Phenylketonuria is inherited in an autosomal recessive manner. This means that both parents either have to have phenylketonuria or be carriers of it for the child to have it.

    Because the condition has a 100% chance of being passed down to children when both parents have it, in most cases, children who have PKU are born to parents who don’t have the condition but are carriers of the mutated gene.

    Is PKU A Deletion Mutation?

    Phenylketonuria is an autosomal recessive metabolic disorder that’s caused by mutations of the PAH gene. In most cases, this is inherited from one’s parents. However, large deletions account for up to 3% of the PAH mutations.

    Is Phenylketonuria Hereditary?

    Phenylketonuria is hereditary. It’s caused by a mutation of the PAH gene, which can be passed from parent to child. However, it’s only certain that your child will have phenylketonuria if both you and your partner have it.

    If only one parent has PKU, the child will be a carrier, but not actually have the condition. Children can also inherit phenylketonuria if both parents are carriers of the mutated gene, but it’s not 100% certain children with parents who are carriers will, in fact, inherit the condition.

    What Are The Chances That I Will Pass Phenylketonuria On To My Child?

    The chance that you’ll pass phenylketonuria on to your child depends on both you and your partner. Children inherit one of each gene from their mother and one of each gene from their father.

    If you have phenylketonuria, you have two mutated PAH genes. If you are a carrier of PKU but don’t have it, you only have one mutated PAH gene.

    So if you and your partner both have phenylketonuria, your child will inherit two mutated PAH genes — they will have phenylketonuria too. If only one parent has PKU, the child will only inherit one mutated gene.

    This means the child will be a carrier of PKU and can pass it on to their children, but they won’t have it.

    If you and your partner are both carriers of the mutated gene but don’t have PKU, you have a:

    • 75% chance your child won’t have PKU
    • 50% chance your child won’t have PKU but will be a carrier
    • 25% chance your child will have PKU
    • 25% chance your child won’t have PKU and won’t be a carrier

    If only one parent is a carrier of phenylketonuria, the child won’t have PKU, but still has a slight risk of becoming a carrier.

    If I Have One Child With Phenylketonuria Will All My Children Have It?

    If you have one child who was born with phenylketonuria, it doesn’t necessarily mean that all your children will have it. It depends on whether you and your partner have PKU yourselves or you’re simply a carrier of the gene mutation that causes the disorder.

    If you and your partner both have phenylketonuria, your child will have it too — all of them. However, if you and your partner are both carriers of PKU, the risk of passing it on to your children is only 25%.

    So you could have one child with the condition and another without it.

    Who Does Phenylketonuria Typically Affect?

    Phenylketonuria affects males and females equally. It’s typically diagnosed shortly after a baby is born, but if it’s not diagnosed during the newborn phenylketonuria test, infants with PKU normally show signs of the disorder within the first few months.

    The PKU incidence rate in the U.S. is only 0.01%. However, infants have a one in four chance of developing phenylketonuria when both parents are carriers of the mutated gene.

    Phenylketonuria is most commonly seen in people of European or Native American descent. While phenylketonuria inheritance is possible within any race, it’s much less common among people of Hispanic, Asian, or African American descent.

    Also, even though PKU is usually a childhood disorder, there are rare cases of adult-onset phenylketonuria. When adult-onset phenylketonuria occurs, it’s normally caused by rapidly progressive Parkinson’s disease or dementia.

    Diagnosis of Phenylketonuria

    A phenylketonuria diagnosis is typically determined at birth. In the U.S. all newborns are tested for PKU when their initial blood work is completed.

    In rare cases, an infant might pass the phenylketonuria test at birth. However, if this happens, the baby will typically develop PKU symptoms within the first few months of life, and another blood test can be performed.

    Adults with rapidly progressing Parkinson’s disease or dementia can also get phenylketonuria. Like with infants, the diagnosis comes from blood work.

    How Do You Diagnose Phenylketonuria?

    If phenylketonuria isn’t found at birth and your child shows signs of developmental delays, your doctor may order an additional phenylketonuria test.

    The test involves taking a blood sample, which is then sent to the lab for testing. To confirm or discount a diagnosis of phenylketonuria, the lab analyzes the blood sample looking for the enzyme responsible for breaking down phenylalanine hydroxylase.

    How Do Doctors Test for Phenylketonuria?

    All infants are required to have a health screening for phenylketonuria when they are one or two days old. In most cases, this screening catches PKU, allowing the doctor to treat it immediately in an effort to avoid severe symptoms of the condition.

    If phenylketonuria doesn’t show up in the initial screening and a child or adult starts showing signs of developmental delays or intellectual disorders, the doctor has to order a blood test to confirm or rule out a PKU diagnosis.

    Genetic Tests for Phenylketonuria — Are they available?

    Newborn screenings identify almost all cases of phenylketonuria. However, if you have a family history of PKU, your doctor may recommend a genetic test to determine whether you’re a carrier of the mutated gene before you begin trying to have a child.

    DNA Tests Currently Available For Phenylketonuria Include:

    • Newborn screenings are completed between 24 and 72 hours after birth to test for PKU
    • Blood tests are typically used to determine if someone is a carrier for PKU or if an infant who passed the screening actually has PKU
    • Amniocentesis is used during pregnancy if there’s a risk of the baby having PKU
    • Chorionic villus sampling can be used to test babies for PKU during pregnancy

    DNA Testing To Spot Or Detect Phenylketonuria Early

    Newborn screenings test for phenylketonuria in babies between 24 and 72 hours old. In most cases, they accurately detect the chromosome mutation so treatment can begin before any major medical issues arise.

    Other tests to detect phenylketonuria early include amniocentesis or chorionic villus sampling, both of which are completed during pregnancy.

    Testing For Phenylketonuria On a Pregnancy Or Before a Pregnancy Is Achieved

    If you have phenylketonuria, you may be worried about passing it on to your child. This is definitely a concern because phenylketonuria is a condition that’s inherited.

    Are There Prenatal Tests For Pku?

    Phenylketonuria can be diagnosed before your baby is born. A prenatal phenylketonuria test is completed using amniocentesis or chorionic villus sampling.

    However, this testing is only completed when both parents are carriers of phenylketonuria or one parent has PKU and the other is a carrier. This is because when only one parent is a carrier of the mutated gene or has PKU, the child won’t have the condition, but could be a carrier of it.

    Where Can I Go for a Genetic Test for My Child?

    Newborns are tested for PKU during their regular newborn screening.

    If, in the rare case, your child tests negative for the condition and develops symptoms later, your doctor will order a DNA test. This is typically completed via bloodwork at your doctor’s office or a lab.

    Is Phenylketonuria Treatable?

    Phenylketonuria treatment involves a restricted diet to limit the amount of phenylalanine hydroxylase in your bloodstream. This means avoiding or strictly limiting:

    • Milk and all other dairy products, including yogurt, cheese, and ice cream
    • Meat and poultry
    • Fish
    • Eggs
    • Nuts and peanut butter
    • Dried beans
    • Regular flour
    • Regular infant formula
    • All foods and drinks made with the artificial sweetener aspartame

    Phenylketonuria Treatment Options:

    In addition to a strict diet, people with PKU may need to:

    • Regularly track Phe levels
    • Take BH4 supplements
    • Only consume medical versions of things like flour, bread, baking mixes, and pastas that are specifically made for people with PKU

    Infants with PKU should only be given medical-grade formula made specifically for babies with PKU.

    What Happens If PKU Is Left Untreated?

    If PKU is left untreated, it can result in irreversible brain damage. It could also impact a person’s neurological system, leaving him or her prone to seizures or tremors.

    What Are Phenylketonuria Care Options?

    People with phenylketonuria have to follow a strict diet for the rest of their lives. They also may need to take BH4 supplements. Babies with PKU can be given medical-grade formula made specifically for infants with PKU.

    The Prognosis for Phenylketonuria

    Many people worry about possible phenylketonuria outcomes, but that isn’t necessary. People living with PKU have to deal with it their entire lives.

    However, as long as they follow a PKU-approved diet and monitor their Phe levels regularly, phenylketonuria should not affect their life expectancy rates.

    Does Phenylketonuria Go Away?

    Phenylketonuria doesn’t go away. It’s a life-long condition that requires you to remain on a strict diet.

    Is There a Cure for Phenylketonuria?

    There isn’t a cure for phenylketonuria. However, by adhering to a strict diet, people with PKU can lead long, fulfilling lives.