Phenylketonuria is caused by a lack of the enzyme needed to convert phenylalanine to tyrosine.
Symptoms include intellectual disability, seizures, nausea, vomiting, an eczema-like rash, and a mousy or musty body odor.
The diagnosis is based on a blood test.
Children who are diagnosed and treated early should develop normally.
A strict phenylalanine-restricted diet allows for normal growth and development.
Amino acids Branched-Chain Amino Acids Amino acid metabolism disorders are hereditary metabolic disorders. Hereditary disorders occur when parents pass the defective genes that cause these disorders on to their children. In most... read more are the building blocks of proteins and have many functions in the body. The body makes some of the amino acids it needs and gets others from food. Phenylketonuria (PKU) is a disorder that causes a buildup of the amino acid phenylalanine, which is an essential amino acid (one that cannot be made in the body but must be consumed in food). Excess phenylalanine is normally converted to tyrosine, another amino acid, and eliminated from the body. Without the enzyme that converts it to tyrosine, called phenylalanine hydroxylase, phenylalanine builds up in the blood and is toxic to the brain, causing intellectual disability Intellectual Disability Intellectual disability is significantly below average intellectual functioning present from birth or early infancy, causing limitations in the ability to conduct normal activities of daily... read more .
There are different types of inherited disorders Inheritance of Single-Gene Disorders Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are made of a very long strand... read more . In PKU, both parents of the affected child carry a copy of the abnormal gene. Because usually two copies of the abnormal gene are necessary for the disorder to occur, usually neither parent has the disorder. (See also Overview of Hereditary Metabolic Disorders Overview of Hereditary Metabolic Disorders Hereditary metabolic disorders are inherited genetic conditions that cause metabolism problems. Heredity is the passing of genes from one generation to the next. Children inherit their parents'... read more .)
Symptoms of PKU
Newborns with PKU rarely have symptoms right away, although sometimes they are sleepy or eat poorly. Symptoms develop slowly over several months as phenylalanine builds up in the blood. If not treated, affected infants progressively develop intellectual disability over the first few years of life, which eventually becomes severe. Other symptoms include
Nausea and vomiting
Lighter skin, eye, and hair color than their family members
Aggressive or self-injurious behavior
Sometimes psychiatric symptoms
Untreated children with phenylketonuria often give off a mousy or musty body odor in their urine and sweat. This odor is the result of phenylacetic acid, which is a by-product of phenylalanine.
Diagnosis of PKU
Newborn screening test
Prenatal screening tests
Phenylketonuria is usually diagnosed with a routine newborn screening test Newborn Screening Tests Many serious disorders that are not apparent at birth can nonetheless be detected by various screening tests. Early diagnosis and prompt treatment can reduce or prevent many disorders that may... read more .
PKU occurs in most ethnic groups. If PKU runs in the family and DNA is available from an affected family member, the prenatal screening tests amniocentesis Amniocentesis Prenatal diagnostic testing involves testing the fetus before birth (prenatally) to determine whether the fetus has certain abnormalities, including certain hereditary or spontaneous genetic... read more or chorionic villus sampling Chorionic Villus Sampling Prenatal diagnostic testing involves testing the fetus before birth (prenatally) to determine whether the fetus has certain abnormalities, including certain hereditary or spontaneous genetic... read more with analysis of DNA DNA Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are structures within cells... read more (the building blocks of genes) can be done to determine whether a fetus has the disorder.
Parents and siblings of children with PKU can be tested to find out whether they carry the gene that causes the disease. If two carriers conceive a child, that child has a 1 in 4 chance of being born with the disease. Carriers Carrier Screening Genetic screening is used to determine whether a couple is at increased risk of having a baby with a hereditary genetic disorder. Hereditary genetic disorders are disorders of chromosomes or... read more are people who have an abnormal gene for a disorder but who do not have symptoms or visible evidence of the disorder.
Prognosis for PKU
Children who are treated in the first few days of life do not develop the severe symptoms of phenylketonuria. A phenylalanine-restricted diet, if started early and maintained well, allows for mostly normal development. However, even with very good control of the diet, affected children still may develop mild mental health problems and may have difficulties in school. Dietary restrictions started after 2 to 3 years of age may control extreme hyperactivity and seizures and raise the child’s eventual intelligence quotient (IQ) but do not reverse intellectual disability. Recent evidence suggests that some intellectually disabled adults with PKU (born before newborn screening tests were available) may function better when they follow the PKU diet.
A phenylalanine-restricted diet should continue for life, or intelligence may decrease and neurologic and mental problems may ensue.
Children who are born to mothers who have poorly controlled PKU (that is, they have high phenylalanine levels) during pregnancy are at high risk of developing an abnormally small head ( microcephaly Microcephaly Microcephaly is an abnormally small head. Often the head is small because the brain is small and abnormally developed. Microcephaly can be caused by many disorders including genetic abnormalities... read more ) and developmental problems. This condition is called maternal PKU.
Prevention and Treatment of PKU
To prevent intellectual disability, people must restrict phenylalanine intake (but not eliminate it altogether because people need some phenylalanine to live) beginning in the first few weeks of life. Because all natural sources of protein contain too much phenylalanine for children with PKU, affected children cannot have meat, milk, or other common foods that contain protein. Instead, they must eat a variety of products that are specially manufactured to be phenylalanine-free. Low-protein natural foods, such as fruits, vegetables, and restricted amounts of certain grain cereals, can be eaten.
Special nutritional products, including infant formula without phenylalanine, are also available. Examples of these special products include PKU Anamix®, XPhe Maxamaid®, and XPhe Maxamum®; Phenex®-1 and Phenex®-2; Phenyl-Free® 1 and Phenyl-Free® 2; pku 1, pku 2, and pku 3; PhenylAde® (varieties); PKU Lophlex® LQ; and Phlexy-10®.
Women who have PKU and who are planning on becoming pregnant should follow the recommended diet and keep their PKU under control.
Doctors may give supplements of the amino acid tyrosine and a drug called sapropterin. This drug helps increase a person's tolerance of phenylalanine.
The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
National Organization for Rare Disorders (NORD): This resource provides information to parents and families about rare diseases, including a list of rare diseases, support groups, and clinical trial resources.
Genetic and Rare Diseases Information Center (GARD): This resource provides and easy to understand information about rare or genetic diseases.