Phenylketonuria: Symptoms, Causes and Treatment

PKU, sometimes called phenylketonuria, is a rare genetic disorder that causes the body to accumulate the amino acid phenylalanine. PKU is caused by a mutation in the phenylalanine hydroxylase (PAH) gene. This gene is involved in the synthesis of the enzyme that degrades phenylalanine.

When eating meals high in protein or artificial sweeteners like aspartame, a person with PKU may face a dangerous build-up of phenylalanine since they do not have the enzyme to break this material down. This might eventually lead to serious health problems.

For the rest of their lives, babies, children, and adults with PKU must eat a diet low in phenylalanine, which is usually found in foods high in protein. Thanks to modern therapies, some PKU patients may be able to consume a diet with a higher or infinite amount of phenylalanine.

In the United States and many other countries, newborns are tested for PKU shortly after birth. Although PKU cannot be cured, early discovery and treatment can prevent major health problems and intellectual disability, or deficits in thinking, understanding, and communicating.

Symptoms Of Phenylketonuria

Newborns with PKU initially show no symptoms. However, PKU symptoms frequently manifest in babies within a few months when treatment is not administered.

The following list of untreated PKU symptoms can range in severity from mild to severe:

• A musty smell in the breath, urine, or skin that comes from the body having too much phenylalanine neurological problems that might cause seizures.
• Because phenylalanine cannot be converted into melanin, the pigment that governs skin tone and hair color, it results in skin rashes similar to dermatitis that are lighter than the skin, hair, and eye colors of family members.
• Microcephaly, or very small head-size disturbance
• Mental illness impeded advancement
• Behavioral, emotional, and social problems
• Disorders of the nervous system
• Different intensities

Based on the kind, PKU might vary in severity.

• Classic PKU. The most severe form of PKU is referred to as classic PKU. The amount of enzyme needed to break down phenylalanine is either negligible or nonexistent. As a result, large amounts of phenylalanine are generated, which might be extremely harmful to the brain.
• Less severe PKU variants. Phenylalanine levels are lower and there is less risk of significant brain damage in weak or moderate variants of the enzyme since it is still partly functioning.

For most infants, kids, and adults with PKU, a specific diet is still required to prevent cognitive impairment and other side effects, regardless of the illness's type.

Pregnancy and PKU

A variation of PKU known as maternal PKU can arise in pregnant PKU mothers. If women do not follow the specific PKU diet, blood phenylalanine levels may increase during pregnancy and pose a risk to the developing child.

Even in situations of less severe PKU, a mother may endanger her unborn child if she follows the PKU diet.

Children born to mothers with high phenylalanine levels do not often inherit PKU. However, if the mother has high blood phenylalanine levels throughout her pregnancy, the child may have serious problems. The baby might have had:

• Low birth weight
• Small head
• Heart problems

The offspring of a mother with PKU may also have delayed development, intellectual impairment, and behavioral problems.

Also Read: Amino Acid Disorders

Causes  Of Phenylketonuria

A genetic mutation that causes PKU might be mild, moderate, or severe. A mutation in the phenylalanine hydroxylase (PAH) gene causes a person with PKU to have reduced or inadequate amounts of the enzyme needed to metabolize the amino acid phenylalanine.

A potentially dangerous phenylalanine buildup may happen in a person with PKU if they ingest foods strong in protein, such as milk, cheese, nuts, or meat; grains, such as bread and pasta; or aspartame, an artificial sweetener.

Inheritance

The mutated gene has to be present in both the mother and the father for a child to be born with PKU. This kind of inheritance is known as autosomal recessive.

A parent can have the gene that causes PKU without really experiencing the illness. If just one parent inherits the mutated gene, the child may be a carrier of PKU even when there is no probability of PKU transmission.

Children with PKU are usually born to two parents who are not aware that they are carriers of the mutated gene.

Also Read: All Important Things About Carbohydrate Metabolism

Risk factors  Of Phenylketonuria

The following are some risk factors for hereditary PKU:

• Having a genetic mutation causes PKU in both parents. Two copies of the mutated gene must be inherited from both parents for a child to be afflicted by the condition.
• Has a certain racial or ethnic background. PKU patients are found worldwide in the majority of ethnic groups. But in the US, people with European ancestry appear to have it more often than people with African ancestry.

Also Read: Enzymes Classification, Properties

Diagnosis  Of Phenylketonuria

During newborn screening, the majority of phenylketonuria cases are discovered. All 50 states in the US mandate that babies get screened for PKU. Infants in many other nations are also routinely checked for PKU.

Your healthcare practitioner could advise screening tests before to getting pregnant or giving birth if you have PKU or if there is a family history of the condition. A blood test can be used to determine PKU carriers.

Testing your newborn after delivery

A PKU test is scheduled for one or two days following the delivery of your child. In order to obtain precise findings, the test is carried out 24 hours postpartum, following a meal including some protein.

• A nurse or lab technician will extract a few droplets of blood from your baby's heel.
• A blood sample is examined in a laboratory to check for metabolic disorders such as PKU.
• If you give birth outside of a hospital or are discharged from the hospital soon after, you may need to schedule a newborn screening with your healthcare provider.

If the results of this test indicate that your kid could have PKU:

• Further blood and urine testing may be necessary for your newborn to confirm the diagnosis.
• To identify the PKU gene mutation, you and your child may undergo genetic testing.

Also Read: Amino Acids (Basic, Acidic), Transamination & Proteins

Treatment  Of Phenylketonuria

Early intervention and continuous treatment should be prioritized to prevent intellectual damage and major health problems in the future.

The main treatments for PKU include:

• A diet for life that contains very little phenylalanine-containing food
• Take a special dietary supplement called PKU formula for the rest of your life to guarantee that you get enough essential minerals and protein (free of phenylalanine) for growth and general health
• For certain PKU patients, medication

Every PKU patient has a unique phenylalanine threshold, and this threshold is subject to vary over time. You want to keep your phenylalanine consumption to what your body needs for development and regular physical activities. Your healthcare provider can determine a safe amount by:

• Checking growth charts and food records frequently
• Frequent blood tests to check phenylalanine levels, especially during pregnancy and juvenile development spurts
• Further evaluations of growth, development, and health

You may make the required dietary adjustments, get guidance on managing PKU diet challenges, and better understand the PKU diet with the assistance of a qualified dietitian. You can receive a recommendation for a professional nutritionist from your medical doctor.

Which products and foods should avoid?

A PKU patient can safely ingest very little phenylalanine, hence it's important to avoid any meals heavy in protein, such as:

• Dairy-based eggs
• Cheese 
• Nuts 
• Soy-based products include milk, soybeans, tofu, and tempeh.
• Beans and Peas
• Meats such as fish, chicken, beef, hog, and others
• You'll probably be limited in what grains and vegetables you eat, including potatoes.

Other meals and drinks that should be avoided by adults and kids alike include many diet sodas and other beverages that include aspartame. Certain medications may contain aspartame, and certain vitamins and other supplements may contain skim milk powder or amino acids. Consult your pharmacist about the contents of over-the-counter and prescription medication.

Consult a qualified dietician or your healthcare provider to learn more about your particular dietary needs.

A food product made specifically for people with PKU

PKU patients have a restricted diet, thus they must take certain nutritional supplements to get the elements they need. Amino acids, an essential component of protein, and other nutrients are provided in a safe format by this phenylalanine-free formula for people with PKU.

With the help of your nutritionist and healthcare provider, you may choose the best type of formula.

• Formula for young children. As regular newborn formula and breast milk include phenylalanine, baby PKU sufferers should instead be given phenylalanine-free infant formula. A nutritionist can determine how much breast milk or regular formula to add to the phenylalanine-free formula. The dietician may also provide parents advice on how to choose meals that are nutritious for their kids without going over their daily allowance of phenylalanine.
• Formula for older children and adults. Older children and adults continue to drink a nutritional supplement free of phenylalanine or eat a protein-equivalent formula as directed by a doctor or nutritionist. Your daily dosage of formula is distributed between your meals and snacks rather than being ingested all at once. 
• Although the formula for older children and adults is different from that for newborns, it nevertheless includes the necessary protein without phenylalanine. The formula is followed forever.
  • The restricted food selections and the need for a nutritional supplement might make the PKU diet challenging, especially if you or your child doesn't find it palatable. However, making this lifestyle change with steadfast commitment is the only way to prevent the serious health problems that people with PKU may encounter.

PKU prescription medications

The FDA has approved sapropterin, also referred to as Kuvan, as a medicine for the treatment of PKU. You can take the medicine together with a PKU diet. Patients with PKU who are on medication might not always need to follow a PKU diet. However, not every PKU patient reacts favorably to the drug.

The FDA has authorized a new enzyme treatment called pegvaliase-pqpz for use in circumstances when the current medicine is not effective in lowering the quantity of phenylalanine in persons with PKU. However, because of the frequent side effects some of which can be extremely serious, this medication is only provided as a part of a restricted program under the supervision of competent healthcare experts.

Also Read: Fat Soluble Vitamins

Prevention  Of Phenylketonuria

If you are trying to get pregnant and are suffering from PKU follow a few of the things mentioned below: 

• Eat a diet lower in phenylalanine. By starting or adhering to a low-phenylalanine diet before becoming pregnant, women with PKU can protect their unborn child. Pregnancy-safe dietary supplements may offer enough protein and nourishment for those with PKU. Consult your physician before to attempting a pregnancy if you have PKU.
• Take into account getting genetic counseling. Before getting pregnant, you could benefit from genetic counseling if you, a close family member, or your child has PKU. A geneticist who specializes in medical genetics can provide you with further information about the PKU inheritance pattern. The expert may also assist in estimating the possibility that you will become parents to a child with PKU and assist with family planning.

Also Read: Water Soluble Vitamins

Complications  Of Phenylketonuria

If not treated, PKU can lead to issues for adults, kids, and babies. The fetus may suffer if a pregnant PKU woman has high blood phenylalanine levels.

Failure to address PKU may lead to:

• Significant brain injury and intellectual disability manifest in the first few months of life Among the neurological problems are tremors and convulsions.
• Major difficulties with growth and health 
• Problems relating to behavior, emotions, and social relationships in older children and adults
• Major issues about growth and wellbeing

Also Read: Lipids: Classification, Pufas, Lipoproteins, Ketone Body Synthesis & Utilization

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