Phenylketonurie (PKU) is an inherited metabolic disorder and also the first treatable metabolic disorder. In PKU the enzyme phenylalanine hydroxylase (PAH) does not work properly which results in the storage of the amino acid phenylalanine in the body which is very harmful for the brain. 

There are two types of phenylketonuria (PKU). The phenylalanine hydroxylase enzyme might not work properly because of: 

• an error in the DNA which prevents the enzyme from being produced properly;
• the molecule BH4 not being produced properly. This molecule needs to activate the phenylalanine hydroxylase enzyme.

In first case we speak of classic PKU. In the second case we speak of BH4 deficiency. 

Next to this, there are also mild forms of PKU, which are called hyperphenylalaninemia. 

PKU is a disorder that presents from birth and has an incidence in North European countries of approximately one in 18,000 births. 

The cause of PKU lies within the DNA. Because of an defect in the PAH gene, the enzyme phenylalanine hydroxylase is missing or does not work properly, preventing the body from breaking down the amino acid phenylalanine. This will result in elevated concentrations of phenylalanine in the blood.    

Patients with BH4-deficiency cannot produce the molecule BH4 properly which also results in the body not breaking down the amino acid phenylalanine. 

Babies with PKU seem perfectly healthy at birth. Without treatment the first symptoms will present around 6 months of age. Babies show a retardation in the mental development. Other symptoms can be: 

• Epilepsy.
• Small head size.
• Light skin and hair color.
• Behavioral problems
• Increased / weak muscle tone

When PKU is detected in time and is treated properly, symptoms can be avoided. 

In the Netherlands, newborn babies are being screened for phenylketonuria via the heel prick test. When high levels of phenylalanine are measured in the blood, additional tests are needed to confirm a diagnosis with additional blood and urine tests. These additional tests will show if the problem lies with the phenylalanine hydroxylase enzyme or with the production of the BH4.   

Treatment of the classic form of PKU exists of following a strict low protein diet and avoiding a sweetener called aspartame. This is due to the fact that the amino acid phenylalanine can be found in protein and aspartame. How strict the diet needs to be, depends on the activity of the phenylalanine hydroxylase enzyme in the body. Because daily protein intake is an important part of a healthy diet, patients with PKU need to consume protein substitutes which do not contain phenylalanine. Patients with PKU follow this special diet under the guidance of the dieticians at our center.

Patients with the BH4 deficient form of PKU are treated with the medicine called KUVAN to lower the patient’s phenylalanine levels. These patients follow a less stricter diet and in some cases a low protein diet is not necessary at all.

All patients with PKU need to do regular blood tests to check their phenylalanine levels. These blood tests are done during the patient’s visit to our outpatient clinic. Next to this, patients with PKU need to measure their bone density every 5 years with a so-called DEXA scan. This is done, because patients with PKU can have decreased bone mineral density.

Pregnant women with PKU receive intensive support at our center to make sure their phenylalanine levels stay stable during their pregnancy. With good phenylalanine levels, the baby will develop normally. Sometimes, it is necessary to admit a pregnant woman for a short period of time. 

Until the age of 18, the metabolic pediatrician is the main caregiver. After this, the patient will be transferred to the metabolic internist. Depending on the age and problems that may arise, patients visit the outpatient clinic several times a year. Your main caregiver works closely with the metabolic dietician. You will see both of them during your visits to the outpatient clinic. 

All pregnant women with PKU will be referred to the gyneacologist who will closely monitor the child's growth and development. After birth, the children are referred to the metabolic pediatrician who will monitor their development for a period of time. 

Please also visit our team page, to meet the specialist at our center.