What is Phenylketonuria?

The disorder is the result of a genetic mutation that prevents phenylalanine being converted to tyrosine, another amino acid. In the presence of this mutation, phenylalanine is converted into phenylpyruvate (phenylketone), and the body is deficient in tyrosine.

Phenylalanine is a large neutral amino acid, and is able to cross the blood-brain barrier via a transporter that processes only large neutral amino acids. Phenylalanine therefore competes with other large neutral amino acids that must also cross the blood-brain barrier. Because there is an abnormally large concentration of phenylalanine, this amino acid tends to saturate the transporters, preventing other amino acids from being transported.

This leads to a deficiency of several amino acids in the brain, and neurotransmitter and protein synthesis cannot proceed normally. The end result is that brain development is disrupted. If phenylketonuria is not diagnosed soon after birth, irreversible damage is done to the brain, causing intellectual disability. Other serious problems can also occur.

Symptoms of Phenylketonuria

Children who are born with phenylketonuria usually appear normal for several months after birth; however unless the disorder is diagnosed, they will begin showing the following symptoms:

· Intellectual development is delayed due to permanent intellectual disability.

· Behavioral problems, seizures, and psychiatric disorders are common.

· Excess phenylalanine often causes a mouse-like odor.

· Children often have lighter hair and skin than family members who don’t have the disorder. Skin disorders such as eczema are common.

Phenylketonuria Treatment

In most developed countries, babied are screened for phenylketonuria soon after birth, often within 24 hours. Repeat tests are usually done two weeks after birth to verify the results.

Unlike most other genetic disorders, phenylketonuria can be completely controlled with dietary modification. Phenylalanine intake must be kept very low, and tyrosine intake must be increased with supplements. This can be somewhat difficult to do, as phenylalanine is present in high levels in all sources of animal protein and some sources of plant protein too.

In the past people with phenylketonuria had been allowed to relax the dietary restrictions after the age of 18. However, the current recommendation is that they manage their levels of phenylalanine for life.

Another concern is that women with phenylketonuria must take care to keep their phenylalanine levels very low before, during, and after pregnancy. In women with phenylketonuria the uterine environment can have very high phenylalanine levels, and this amino acid can cross the placenta. High levels of phenylalanine in utero can lead to birth defects such as heart disease, intellectual disability, and growth retardation.

References

Medline: Phenylketonuria

Phenylketonuria Information at the National Institute of Health

Georgianne L Arnold, MD. Phenylketonuria at eMedicine