1.The etiology of phenylketonuria
PKU (phenylketonuria) is a metabolic genetic disorder. If left untreated, it can cause mental retardation. Fortunately, with routine newborn screening, almost all affected newborns can now be diagnosed and treated early to ensure normal mental development.
The prevalence of phenylketonuria is 1 in 14,000 in the U.S. Although the disease is more prevalent in Northern European and Native American individuals than in African Americans, Hispanics, and Asians, it can occur in all ethnic groups.
Due to enzyme loss or defects, children with phenylketonuria are unable to fully metabolize phenylalanine protein, which is present in almost all foods. If left untreated, phenylalanine can build up in the blood of affected newborns and cause brain damage and mental retardation.
2. How does phenylketonuria affect the child?
Children with phenylketonuria can be normal for the first few months of life. If left untreated, they begin to lose interest in their surroundings between 3 and 6 months of age, and by 1 year of age, their development is significantly delayed. Children with untreated Phenylketonuria whose central nervous system is already damaged are often irritable, agitated and disruptive. Their physical development can be better and their hair is often more yellow than that of their siblings.
3. Who is at risk for phenylketonuria?
When both parents have the phenylketonuria gene and both pass it on to their children, their children will inherit phenylketonuria. If the father or mother has the Phenylketonuria gene but does not develop the disease, they are called “carriers”. In carriers, there is both a normal gene and a phenylketonuria gene in each cell. Carriers do not have any health effects.
When both parents are carriers, there is a 1 in 4 (25%) chance that they will pass on the phenylketonuria gene to their child and cause the child to be born with phenylketonuria. In addition, there is a 1 in 4 chance that both parents will pass on the normal gene, and the child will be neither sick nor a carrier and will be completely normal. Remember, these odds are the same for every pregnancy.
4. Do all babies need to be screened for phenylketonuria?
Screening for phenylketonuria is already available in the vast majority of countries. Every newborn baby is screened before leaving the hospital. The first newborn screening was done in the United States, and since the 1960s it has been used as a routine screening test, saving thousands of affected children from developing mental retardation.
5. How is this test done?
A few drops of blood are collected from the baby’s heel with a needle (the same specimen can be used to screen for many other inborn metabolic disorders), and the blood sample is often sent to a local medical laboratory for testing to find out if the phenylalanine level in the blood is higher than normal. If the results are not normal, then additional tests are done to determine if the baby has phenylketonuria or if other factors are affecting phenylalanine levels.
This test is done within 24 hours to 7 days after birth and is more accurate. However, early discharge is becoming more common, and many infants are being tested within 24 hours of birth. Because some phenylketonuria may be missed by doing this test early, the American Academy of Pediatrics recommends that infants who have been tested within 24 hours of birth should be tested again between 1 week and 2 weeks after birth.
6. Can the symptoms of phenylketonuria be prevented?
Yes. Mental retardation can be avoided if the infant is treated with a low-phenylalanine diet starting 7 to 10 days after birth.
Initially, the infant is fed a special formula that contains protein but no phenylalanine. Breast milk or infant formula is fed in small amounts to provide only the amount of phenylalanine that the infant can tolerate. Subsequently, some vegetables, fruits, cereal products (such as cereal and pasta) and other low-phenylalanine foods may be added to the diet, but regular milk, cheese, eggs, meat, fish and other high-protein foods should not be fed. Protein is essential for normal growth and development, so children must be continuously fed special formulas that are high in protein and essential nutrients but contain little or no phenylalanine. Beverages and foods spiked with artificial desserts (aspartic acid methyl phenylalaninate) must also be avoided at all costs.
Children and adults with phenylketonuria should be followed up by medical centers specializing in the treatment of phenylketonuria. Each patient’s diet must be individualized, based on phenylalanine tolerance, age, weight, and other factors. All patients should have regular blood tests to determine if their phenylalanine levels are too high or too low. This can be done once a week for infants up to one year of age and once or twice a month throughout childhood. The diet must be adjusted accordingly to the test results.
Patients with phenylketonuria must consume a low-phenylalanine diet throughout childhood and adolescence, and generally throughout their lives (although patients can sometimes go without this restricted diet as adults). Until the 1980s, doctors believed that around the age of 6, when the brain has matured, children with phenylketonuria could safely discontinue their special diet. However, most children with phenylketonuria who have high blood levels of phenylalanine during childhood and adolescence will have reduced intelligence, decreased learning ability, and abnormal behavior.
Parents and adults with Phenylketonuria should discuss their diet and treatment with their Phenylketonuria specialist clinician.
7. What is maternal phenylketonuria?
In the United States, an estimated 3,000 cases of women of childbearing age with phenylketonuria have been successfully treated. Most of them had their special diet interrupted during childhood, when many doctors thought it was safe.
If these women were currently eating a regular diet, they would have had very high blood phenylalanine levels when they became pregnant, which would have damaged the fetus. 90 percent of the babies would have suffered from mental retardation and/or microcephaly, and many would have had heart defects, low weight and characteristic facial features. These babies do not inherit phenylketonuria, but rather the fetal brain is completely damaged due to high phenylalanine levels in the mother’s blood, so treating these babies with a special diet is useless.
Fortunately, there is a way to help the babies of women with phenylketonuria from mental retardation and other problems. These women of childbearing age need to restart the special diet in the first trimester of pregnancy and continue it throughout the pregnancy. This controls the phenylalanine levels in the blood of pregnant women so that they can have a healthy baby. They must have a blood test at least once a week throughout their pregnancy to ensure that their blood phenylalanine levels are not too high.
The U.S. recommends that young women who are known or suspected to have been treated for phenylketonuria as children contact their physicians before deciding to become pregnant so that their blood phenylalanine levels can be tested and, if necessary, they can be put back on a special diet.
Phenylketonuria is not diagnosed in individual women, who are usually not screened during the neonatal period usually and are less impaired, and may only be diagnosed after the birth of a child with a birth defect related to phenylketonuria. To combat the development of these birth defects, some physicians recommend screening women who are at risk for Phenylketonuria (such as those with a family history of Phenylketonuria) so that women with the disease can begin eating a special diet for Phenylketonuria before they become pregnant.
8. What are the latest studies on phenylketonuria?
The long-term outcomes of children of treated pregnant women with phenylketonuria are being studied. Although these children do not usually have birth defects, it is important to find out if the cognitive potential of these children is fully developed. There is also some research being done to synthesize the missing enzyme, which may eventually allow individuals with the disease to eat a more normal diet. Some studies are also exploring the feasibility of treating phenylketonuria with gene therapy.