Phenylketonuria (PKU) is a rare genetic disorder that results in excessive accumulation of the amino acid, phenylalanine, and reduced levels of the amino acid, L-tyrosine, in the blood.1
If untreated, high levels of phenylalanine can cause severe mental retardation, behavioral disturbances, and other brain and nerve problems. Fortunately, newborn screening programs now identify most cases of PKU in the United States and other countries. Early diagnosis and treatment is the key to reducing or preventing PKU-related conditions.2 Gene therapy is currently being researched as a possible cure.3 4 Research is also being conducted on methods to decrease levels of phenylalanine in the blood through the use of certain enzymes5 and amino acids.6
What are the symptoms of phenylketonuria?
Infants with PKU may be lethargic, feed poorly, and have a “mousy” odor from their sweat and urine. Eczema, sensitivity to sunlight, and light skin are also characteristic of PKU. Symptoms of children with untreated PKU include significantly diminished mental capacity, hyperactivity, and seizures.
Dietary changes that may be helpful for phenylketonuria
PKU can be controlled by a diet low in phenylalanine.7 The greatest benefits are achieved when the diet is started in the first few days of life,8 although later treatment will still help to reduce the severity of PKU-related conditions.9 10 11 Maintaining low phenylalanine levels through dietary control improves muscle control and behavioral and intellectual function.12 13
The effects of elevated phenylalanine appear to be less severe in older children and adults than in newborns and young children, in whom the nervous system is still developing. This, combined with the difficulties inherent in following a strict lifelong diet, have caused researchers to examine whether the dietary regimen may be relaxed as children get older. While some research suggests that relaxation of dietary measures may not be harmful,14 15 16 this has not been found to be true in all studies.17 Therefore, more research is needed to resolve this issue.18 19 In a survey of 111 PKU treatment centers, 87% favored lifelong dietary restriction of phenylalanine.20 The PKU diet is strict, and should be undertaken with the help of a nutritionist and a physician.
Breast-feeding, as opposed to formula feeding, appears to confer some benefits in children born with PKU who were not treated until 20–40 days of age. In a preliminary study, children with PKU who had been breast-fed rather than formula fed prior to receiving dietary treatment scored significantly higher on IQ testing.21 Infants with PKU tend to retain abnormal amounts of the trace mineral molybdenum. Since infant formulas are supplemented with amounts of molybdenum that far exceed amounts found in breast milk, infants with PKU who are also fed formula run the risk of accumulating excessive molybdenum.22
A PKU diet is low in protein, providing no more than the minimum amount of phenylalanine needed by the body. All high-protein foods, such as dairy products, eggs, fish, meats, poultry, legumes, and nuts, are usually eliminated.23 Lower protein foods, such as fruits, vegetables and some grain products, are allowed in measured amounts, along with specially prepared phenylalanine-free or nearly phenylalanine-free foods. This diet is supplemented with an amino acid formula to increase protein intake without adding more phenylalanine than is nutritionally required.
Phenylalanine levels fluctuate as a consequence of changes in diet, health, and growth; therefore, levels must be checked regularly.24 A nutrition specialist can also provide information on homemade and specially prepared foods for people with PKU, including infant formulas, low protein pastas, breads, crackers, and other foods.
People with PKU who are not following the PKU diet can become deficient in biotin, a water-soluble B vitamin. This is because phenylalanine blocks biotin metabolism. In a controlled study of children with PKU, elevated phenylalanine levels resulted in seborrheic dermatitis caused by biotin deficiency, which was corrected by a return to the phenylalanine-restricted diet.25
There is debate about whether it is safe for people with PKU to consume aspartame, a low-calorie sweetener that contains about 50% phenylalanine. In one study, blood levels of phenylalanine increased only slightly after people with PKU ingested a 12-ounce soft drink sweetened with aspartame.26 However, that study did not address long-term effects of regular aspartame consumption. Until more is known, it is prudent for people with PKU to completely avoid aspartame-containing beverages and foods.
Lifestyle changes that may be helpful for phenylketonuria
Access to PKU resource/support groups, and education of family members may help simplify the complex dietary restrictions and improve one’s ability to follow them.27 28 29
PKU during pregnancy (maternal PKU) is of particular concern. Excessively high or low levels of phenylalanine may occur during pregnancy, both of which may adversely affect the fetus.30 Maternal PKU can lead to fetal malformations, including small head size (microcephaly), heart abnormalities, failure to grow properly in the uterus (called intrauterine growth retardation), and mental retardation.31 Adverse effects on the offspring can be reduced and by careful dietary control both prior to and during pregnancy.32 33 34 Consultation and follow-up visits with medical and nutritional specialists are necessary for effective monitoring and dietary guidance in people with PKU.
Nutritional supplements that may be helpful for phenylketonuria
Because of the importance of strict dietary control, nutritional supplementation should be supervised by a specialist.
In a double-blind trial, regular use of branched-chain amino acids (BCAAs) (i.e., valine, isoleucine, and leucine) by adolescents and young adults with PKU improved performance on some tests of mental functioning.35 Participants received either placebo, or 150 mg per 2.2 pounds of body weight each of valine and isoleucine, and 200 mg per 2.2 pounds of body of leucine, taken with meals and at bedtime. Participants received one mixture or the other for four three-month periods, for a total of six months’ supplementation of each regimen over the course of a year.
PKU results from a deficiency or malfunction of the enzyme, phenylalanine hydroxylase, which converts phenylalanine to L-tyrosine.36 People with PKU have elevated concentrations of phenylalanine and low levels of L-tyrosine,37 which may contribute to behavior problems.38 39 In addition, low L-tyrosine levels in pregnant women with PKU may contribute to fetal damage.40 In some,41 but not all,42 double-blind studies, keeping L-tyrosine levels in the normal range by adding supplemental L-tyrosine to the diet improved behavior. In a preliminary study, blood L-tyrosine levels fluctuated significantly in people with PKU, suggesting a need for careful laboratory monitoring of people supplementing with L-tyrosine.43
The PKU diet is low in fatty acids, some of which are essential for proper brain development.44 In one controlled study of children with PKU who were deficient in fatty acids, supplementation with fish oil (but not with black currant seed oil) for six months improved the deficiency. The children received 500 mg of oil per 8.8 pounds of body weight each day for 6 months. The amount varied from 5–8 capsules (each containing 500 mg) per day for each child.45
People with PKU may be deficient in several nutrients, due to the restricted diet which is low in protein and animal fat. Deficiencies of long-chain polyunsaturated fatty acids (LC-PUFAs),46 47 48 selenium,49 50 51 52 vitamin B12,53 and vitamin K may develop on this diet.54
Selenium is important for normal antioxidant function. Research suggests that selenium deficiency and decreased antioxidant activity may contribute to the brain and nerve disorders associated with PKU.55 In two preliminary studies involving selenium-deficient people with PKU, supplementation with selenium in the form of sodium selenite corrected the deficiency,56 whereas supplementation with selenium in the form of selenomethionine did not.57
Vitamin B12 is found almost exclusively in foods of animal origin, which are restricted on the PKU diet. People on the PKU diet who are inconsistent in their use of a vitamin B12 supplement may become deficient in this vitamin. In a survey of young adults with PKU, 32% were found to have low or low-normal blood levels of vitamin B12.58 Vitamin B12 deficiency can cause anemia and nerve problems.
Because the PKU diet is low in animal products, fat intake is also significantly reduced. The results of a preliminary study of children with PKU suggested that the low-fat PKU diet intake may impair the absorption of vitamin K, a fat-soluble vitamin, from the diet, possibly resulting in a vitamin K deficiency. In that study, children with PKU on a strict diet had low levels of certain vitamin K-dependent proteins needed for normal blood clotting.59
Are there any side effects or interactions with phenylketonuria?
Refer to the individual supplement for information about any side effects or interactions.