Phenylketonuria (PKU) and pregnancy

Phenylketonuria (PKU) is a metabolic disease caused by a genetic mutation.

If not treated immediately, continuously, and appropriately with a special diet, PKU can lead to serious mental health problems, heart problems, seizures, and other physical, skin, and neurological problems.

What is PKU and what causes it?

PKU is a rare autosomal recessive disorder that prevents the body from breaking down one of the amino acids found in almost all proteins: phenylalanine. The affected PAH gene codes for phenylalanine hydroxylase, which converts phenylalanine to tyrosine (another amino acid) in the liver. When this conversion does not occur, phenylalanine accumulates in the blood and causes problems, especially in the brain.

PKU occurs when an abnormal or mutated FAH gene from a mother and father is passed on to a child. Each person has two copies of this gene, one from each parent. Two mutated or deleted FAH genes cause PKU. It can mean one of four things:

The parents are both carriers of 1 copy of the mutated gene each (but do not have the disease)
One parent has the disease and the other is a carrier of a mutated gene
Both parents have the disease, or
One parent is a carrier of a mutated gene and the other abnormal gene came about through a mutation or deletion of the gene of the other’s egg or sperm.

There are a few other common PKU names to be aware of:

Folling’s disease
Phenylalanine hydroxylase deficiency
PAH deficiency

How common is PKU in infants?

If you and your partner's family members have a history of PKU, you may consider genetic counseling to better understand your chances of having a child with PKU.

Typically, if both parents carry the mutated gene (each has a mutated copy), then only 25% of each pregnancy is at risk of developing full disease. This also means that in 50% of cases, each pregnancy can result in the birth of a child who is also a carrier of the mutated gene.

What are the symptoms of PKU?

Typically, a newborn with PKU is identified during newborn screening and treated immediately, meaning they are unlikely to even notice any symptoms. If it is not detected at newborn screening, although it is unlikely, by the time it can be detected by symptoms, the brain damage is often irreversible.

If PKU is not diagnosed and diagnosed shortly after birth, the following symptoms may be found:

Lethargy (weakness)
Poor feeding habits
Vomiting
Irritability
Skin rash with blisters/pimples (eczema-like)
Musty body odor

If not kept on the PKU diet, the following are the most common neurological symptoms:

Seizures
Spastic muscle movements
Hypertonicity (tight muscles)
Increased tendon reflexes
Abnormal electroencephalogram
Physical disability (rare)

How does PKU cause brain damage or mental retardation?

If left untreated or improperly regulated, high levels of phenylalanine in the blood accumulate in the brain. These high levels of phenylalanine cause the breakdown of a fatty, insulating layer called myelin that surrounds nerve fibers in the brain. Without myelin, the nerves cannot fire or communicate properly, resulting in mental retardation.

How is PKU diagnosed?

The test is carried out immediately after the birth of the child and consists in taking a drop of blood from the heel of the child. In this way, the child's caregivers and parents can provide adequate treatment to prevent brain damage.

What types of treatment are available?

The available treatment for phenylketonuria consists of many dietary restrictions. This includes limiting protein intake; however, this must be done with care to prevent mental retardation as well as neurological and dermatological problems. Common foods high in protein and phenylalanine should be avoided:

Dairy (milk, cheese, yogurt, etc.)
Eggs
Nuts, beans, and legumes
Soybeans and peas
Poultry, beef, and pork
Fish and shellfish
Beer (later in life)
The artificial sweetener aspartame

Because the PKU diet does not allow high protein intake, people with PKU may lack essential nutrients. That's why it's important to talk to your doctor and/or dietitian to make sure you or your child are getting all the nutrients they need.

Is there a cure for PKU?

Since phenylketonuria is a genetic disease, there is no cure. Mutations in both copies of the FAH gene are present in every cell of the body of a sick person. As mentioned above, there are treatments that can control the amount of phenylalanine circulating in the body and bring it down to a safe level. Eating a special diet low in phenylalanine (low in protein) can also be a very effective treatment.

As mentioned above, there are treatments available, such as following a special diet low in phenylalanine (low in protein). There are also medications that can control the amount of phenylalanine circulating in the body and bring it down to a safe level.

Are there any other conditions associated with PKU?

Certain conditions can also cause excess phenylalanine in the blood. The disorder most closely associated with PKU is called tetrahydrobiopterin deficiency phenylalaninemia or tetrahydrobiopterin deficiency (BH4). People with this disorder may have perfectly healthy FAH genes but instead have mutations in the gene that codes for BH4, a coenzyme that binds to phenylalanine hydroxylase to help convert phenylalanine to tyrosine. It is also active with other enzymes, and when Phe levels are high, it can lead to a decrease in neurotransmitter levels. This can lead to neurological problems similar to those seen in PKU.

This condition is also rare and requires immediate treatment to prevent long-term neurological and motor problems.

Mothers with PKU

I have phenylketonuria and want to have a baby/I'm already pregnant. Is there a risk to my child?

The risk is highest if the woman is not treated for PKU/does not follow a PKU diet and/or is not taking drugs that lower phenylalanine levels. If a woman is not treated, she may experience problems with pregnancy, such as an increase in spontaneous miscarriages or fetal growth retardation. In addition, pregnant women with untreated phenylketonuria are more likely to have children with microcephaly, congenital heart defects, and facial abnormalities. The association with these problems is higher with higher maternal phenylalanine levels.

It is important to remember that the association with these problems is higher with higher maternal phenylalanine levels. Thus, if you have phenylketonuria, are on treatment, and have your serum phenylalanine levels under control, your chances of having a baby with the above problems are much lower. If you're worried, take the time to talk to your doctor about the steps you need to take before you get pregnant or what you might need to focus on now that you're pregnant. Doctors usually assume that if a woman with PKU wants to get pregnant and doesn't

Doctors recommend that if a woman with PKU wants to become pregnant and is not currently on a PKU-limiting diet or phenylalanine-lowering drugs, start these diets before conception.

If I have a child with PKU, can he breastfeed?

Because breast milk contains a significant amount of protein and therefore phenylalanine, no, it is not considered safe to breastfeed a baby. In this case, the risks of breastfeeding outweigh the benefits. Doctors will prescribe the appropriate formula and medications to help your child maintain a safe level of phenylalanine.

If I have PKU, does that mean my baby will have it too?

Everything depends on the father. If you, as a mother, suffer from classic phenylketonuria (two highly mutated copies of the PAH gene), then you will pass one of these mutated copies to your child, making him a carrier. If the father does not have PKU and does not carry a mutated genetic copy, there is little chance that your child has classic PKU (“nearly no” means it is unlikely that the sperm has a random mutation in this gene). ). If the father is a carrier of the mutated FAH gene, there is a 50% chance that your child has PKU and a 50% chance that the child is only a carrier.