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Newborn screening plays a critical role in detecting PKU, which helps in managing the disease. A blood test detects high Phe levels early. When the baby tests positive for PKU, with diet and medications, it's easy to control the damage and ensure normal development. If not detected early, damage progresses and causes serious problems for the babies.
What is Phenylketonuria
PKU is a rare inherited metabolic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH). This PAH is essential for breaking down the amino acid phenylalanine (Phe), which is found in all protein-rich foods like milk, eggs, meat, and nuts. Phe is converted into tyrosine, an amino acid for neurotransmitter production.
When phenylalanine cannot be metabolised properly, it accumulates in the blood and brain, acting like a toxin that harms developing nerves. Newborns don't show major symptoms, making early screening crucial. If not treated early, the built-up phenylalanine levels affect brain growth and function.
Genetics of PKU
PKU is a genetic disorder which follows an autosomal recessive inheritance pattern. Here, the child must inherit two copies of the faulty gene (PAH) from each parent to develop the disease. Parents who carry one faulty gene become carriers. They don't show any symptoms and have normal Phe levels.
However, when both parents carry faulty genes, there is a 25% chance the child will have PKU, a 50% chance the child will be a carrier, and a 25% chance the child will be unaffected. Genetic testing before conception helps in identifying the risks.
Types of PKU
- Classic PKU: It is the most serious disorder. In classic PKU, the enzyme activity is very low or absent, resulting in high blood phenylalanine levels. Infants with classic PKU are at risk of intellectual disability, seizures, behavioural disorders, and developmental delays.
- Mild PKU: It's when some of the phenylalanine enzymes work 5-30%. Phe raises moderately. However, mild PKU also needs careful treatment, as it can increase and affect cognitive function and neurological development.
How PKU Affects the Baby
Phenylketonuria disrupts the phenylalanine metabolism. In normal people, the PAH enzyme converts phenylalanine into tyrosine, an amino acid essential for neurotransmitter production. If Phe can't be broken down, it piles up in the blood, tissues, and brain.
When it accumulates, it becomes toxic and crosses the blood-brain barrier, interfering with brain development. The accumulated Phe blocks the transport of other amino acids for neurotransmitters, such as dopamine, norepinephrine, and epinephrine.
This slows down protein synthesis and increases harmful reactive oxygen species that damage cells, lipids and DNA. In infants, it affects myelination and energy production, increasing the risk of cognitive delays, seizures and behavioural issues.
Tyrosine is the building block for brain chemicals. The accumulation of Phe increases the toxicity, leading to oxidative stress and poor brain function.
Newborn Screening and Early Diagnosis of PKU
Newborn screening helps catch the disorder early before it starts showing symptoms or affects the baby’s brain.
Universal Newborn Screening
Many countries screen newborns for PKU within the first 24-72 hours after birth. Most newborns with PKU don't show early symptoms, so early screening helps identify elevated phenylalanine levels before the damage begins.
How PKU Testing Is Performed
In newborn screening, they use a heel-prick blood test, where a few drops of blood are collected on special filter paper and sent to a lab where they measure phenylalanine levels.
If the test comes back positive, blood tests are repeated to confirm Phe. A urine test is done to detect abnormal phenylalanine metabolism, and genetic testing helps identify mutations in the PAH gene.
Benefits of Early Diagnosis
Early diagnosis is crucial for PKU, and if positive, treatment should be started from the first week to prevent brain damage. With medicines and diet, it's easy to stop Phe accumulation, which can disrupt nerve growth.
Kids can grow without behavioural issues and normal cognitive development. Early detection reduces long-term health issues.
Symptoms of PKU in Babies
Newborns with PKU mostly show no symptoms and look like a normal, healthy baby at birth. It takes at least 3-6 months to show symptoms because phenylalanine accumulates from milk. During this period, the damage might have started without any symptoms.
As Phe levels increase, the following symptoms start to show:
- Body Odour: A musty body odour or smell in urine or breath appears due to phenylacetic acid.
- Light Skin, Hair, and Eyes: Low tyrosine reduces melanin production, which makes babies fairer, with pale hair and light eyes.
- Developmental Delays: Babies lose interest in toys or people and show a delay in sitting, crawling, and babbling.
- Irritability: Shows more fussiness and jerky movements.
- Small Head: The head grows more slowly due to poor brain development.
- Behavioural Issues: Less eye contact or smiling, and a delay in waking and movement.
Treatment for Phenylketonuria (PKU)
Once detected, PKU should be managed for a lifetime to keep phenylalanine levels normal for growth and brain development.
- Lifelong Diet: Babies have to follow a strict low-phenylalanine diet forever. As babies grow, they can't eat every food. They have to only eat low-Phe fruits and vegetables, and avoid high-Phe foods like meat, egg, dairy, nuts, and legumes.
- Avoid Aspartame: An artificial sweetener in diet sodas, gummies, and candies. It breaks down into Phe during digestion. Babies with PKU should completely avoid these items.
- Medication: Other than diet, doctors might put babies on sapropterin dihydrochloride, which helps increase the tolerance to dietary phenylalanine. For adults, Pegvaliase can help reduce phenylalanine levels.
What Happens If the Mother Has PKU During Pregnancy?
Phenylketonuria during pregnancy can pose a serious threat to pregnant women and foetal health. High phenylalanine levels in the mother's blood can affect the growing baby.
Unlike classic PKU, maternal PKU syndrome happens because high Phe crosses the placenta and acts as a toxin to the developing foetus.
High maternal Phe disrupts foetal brain growth, organ formation, and overall development. Here are some other pregnancy complications PKU causes:
- Low Birth Weight: Babies look small for their gestational age due to impaired nutrition.
- Small Head Size: If PKU goes untreated, it can disrupt brain development.
- Congenital Heart Defects: It can cause structural heart defects, a narrow main artery that carries blood from the heart to the body, create a hole in the wall separating the heart's lower chambers, or cause the left side of the heart to go underdeveloped.
- Intellectual Disability: Babies might have low IQ and face severe behavioural changes.
Phenylketonuria Disease is a serious, rare genetic disorder that can affect a baby's brain and cause long-term problems. Managing PKU from an early age is critical to reduce the damage. Despite medication, dietary restrictions should be followed from birth to avoid symptoms of PKU. PKU cannot be predicted for newborn children, so early screening is crucial.
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FAQs on What Is Phenylketonuria (PKU)? How It Affects Babies
- Can a baby with PKU be breastfed?
Babies with phenylketonuria can be breastfed. Breastfeeding helps with better weight gain and stabilises blood Phe levels. Combining the Phe formula with breastmilk helps keep the baby safe. - What are the behavioural problems associated with PKU?
People with PKU often show ADHD symptoms, anxiety, depression, mood swings, and irritability. They often isolate themselves, experience low self-esteem, and decreased motivation. Sometimes they may also show impulsivity, frustration, and aggressive behaviour.