What is phenylalanine?

Phenylalanine (abbreviated Phe) is an essential amino acid, necessitating its intake through the diet as the human body cannot produce it. It contributes to protein synthesis and undergoes intracellular conversion into tyrosine, a nonessential amino acid. Tyrosine is utilised for various cellular processes including;

• Protein synthesis 
• Production of energy for the body to utilise
• Conversion into the vital neurotransmitters epinephrine, norepinephrine, and dopamine¹

Importance of monitoring phenylalanine levels during pregnancy

Careful pregnancy planning is crucial for women with phenylketonuria (PKU). 

They should maintain a strict low-protein diet and monitor their blood phenylalanine levels before and during pregnancy. Failure to adhere to the diet can lead to high phenylalanine levels in the blood, posing risks to the baby's health, even in early pregnancy stages.

What is phenylketonuria (PKU)?

Phenylketonuria (PKU) is a rare autosomal recessive inherited disorder where the amino acid phenylalanine builds up in the body. The disease is caused by variants in the gene encoding the enzyme phenylalanine hydroxylase (PAH), responsible for converting phenylalanine into tyrosine. When PAH is deficient, phenylalanine levels increase in the blood and brain.

Untreated PKU can lead to irreversible intellectual disability, damage to motor skills, microcephaly (small head size), eczema, autism, seizures, developmental problems, and psychiatric symptoms. 

Since the introduction of newborn screening, early initiation of lifelong treatment has become achievable, leading to normal life for individuals with PKU who receive prompt treatment.^2,3

This article highlights the significance of monitoring phenylalanine levels in pregnant women with PKU. It emphasises the need for a low-protein diet, regular monitoring, and potential medication use to ensure the baby's health during pregnancy.

How is PKU diagnosed?

All newborns are offered screening around day 5 after birth to test for PKU and several other conditions. Upon confirmation of PKU, immediate treatment will be initiated to minimise the risk of serious complications. This typically involves adopting a specialised diet and undergoing regular blood tests. Early diagnosis and proper treatment enable most children with PKU to maintain healthy lives. Approximately 1 in 10,000 babies born in the UK are affected by PKU.

What are the symptoms of PKU? Early initiation of treatment for PKU typically prevents the onset of symptoms. However, without treatment, PKU can result in damage to the brain and nervous system, ultimately causing learning disabilities.

Other symptoms include:

• Behavioural challenges including, frequent temper tantrums and instances of self-harming behaviour
• Fairer skin, hair and eyes, attributed to the body’s failure to transform phenylalanine into melanin
• Eczema
• Repeatably being sick
• Stunted or slow growth
• Jerking movements in arms and legs
• Tremors
• Epilepsy
• Musty smell to the breath, skin and urine, resulting from elevated phenylalanine levels in the body

What are the recommended guidelines and treatment ranges for managing PKU?

Individuals with phenylketonuria (PKU) receive treatment with a phenylalanine-restricted dietand protein substitutes (amino acid supplements) to lower the blood phenylalanine concentrations and prevent the negative effects on the nervous system.

Several guidelines for diagnosing and managing people with PKU have been published. One of the main recommendations is monitoring the phenylalanine-restricted diet, using age-appropriate phenylalanine target treatment ranges, to prevent neurological issues.

In the latest set of guidelines, the following target treatment ranges are recommended:

• 120 to 360 μmol/L for individuals aged 0 to 12 years
• 120 to 600 μmol/L for individuals older than 12 years
• 120–360 μmol/L for women trying to conceive and during pregnancy⁴

Pregnancy and PKU

Pregnant women with PKU are at risk of another form of this metabolic disorder called maternal PKU. If these women don't follow the special phenylalanine-restricted diet before and during pregnancy, blood phenylalanine levels can become elevated and harm the developing fetus.

Even women with a milder form of the condition may still endanger their unborn children by not adhering to the PKU diet.

Babies born to women with elevated phenylalanine levels don’t usually inherit PKU. However, a child can have serious issues if the levels of phenylalanine are high in the maternal blood during pregnancy. 

At birth, the baby may have:

• Low birth weight
• Microcephaly (unusual small head size)
• Congenital heart disease

In addition, maternal PKU can result in delayed development, intellectual disability and behavioural problems in the child.

Planning pregnancies carefully is advised for all women with PKU. They should aim to follow a strict low-protein diet (low phenylalanine) and monitor their blood before becoming pregnant. 

It's best to plan conception once phenylalanine levels are within the target range for pregnancy.

Healthcare providers aim for individuals to monitor their phenylalanine levels three times a week when preparing for pregnancy and during pregnancy so that these should be kept below 300µmol/L.

During pregnancy, they will have frequent contact with a dietitian and the medication sapropterin may also be recommended.

As soon as the baby is born, phenylalanine control can be eased allowing for smooth breastfeeding.

What is the diet for PKU?

 The primary approach to treating PKU is a low-protein diet (referred to as a low phenylalanine diet), along with careful management of other food consumption, including items like potatoes and cereals.

Foods that are high in protein should be completely avoided. These include:

• Meat and fish
• Nuts and seeds
• Eggs and cheese
• Bread, pasta, cakes and biscuits
• Soya and tofu

In this diet, amino acid supplements are necessary to ensure proper nutrient intake.

As long as a person with PKU follows a low-protein diet throughout childhood, and keeps their phenylalanine within certain limits, they will stay healthy and their brain function should be unaffected.

Aspartame

Individuals with PKU must also avoid food products containing aspartame, as it's converted into phenylalanine in the body.

Aspartame is an artificial (chemical) sweetener found in:

• Sugar substitutes such as the artificial sweeteners commonly found in tea and coffee
• Diet drinks
• Chewing gum
• Squash and cordial
• Some alcopops

All food products containing aspartame or a related product should be clearly labelled.

Aspartame is found in certain medications, including children's cold and flu remedies.

Sapropterin

Sapropterin, a medication, may be prescribed alongside a low-protein diet to treat a mild form of PKU known as hyperphenylalaninemia.

For those with hyperphenylalaninaemia, sapropterin may be recommended if they are:

• Under 22 years of age
• Pregnant
• An adult who is likely to respond to treatment (a genetic test is necessary to determine)

 It’s believed that sapropterin may help:

• Lower the level of phenylalanine in the body
• Protect the brain
• Allow to eat a less restricted diet
• Achieve better control of phenylalanine levels than through diet alone

However, the effectiveness of sapropterin in the long term is uncertain. 

Summary

For women with PKU, planning pregnancies, having a low-protein-containing diet whilst checking blood phenylalanine levels is important to prevent severe health issues for the baby. Increased phenylalanine causes issues with growth and other various health complications, therefore managing diet and regular testing are important.