Phenylketonuria, more commonly known as PKU, is an inherited disease that causes a protein called phenylalanine to increase in the body. It usually affects infants. Testing is almost always done shortly after birth that checks for this disease. However, sometimes, when checks are not done, the disease may go unnoticed and develop into a more serious form of PKU.
The PAH gene (phenylalanine hydroxylase) is the gene that the mutation occurs in to cause phenylketonuria. The PAH gene is supposed to convert phenylalanine into tyrosine, but a deficiency of this gene causes high level of phenylalanine to build up in the body. This leads to severe health problems associated with phenylketonuria, such as intellectual disabilities.
This is how the PAH gene works to control phenylalanine and tyrosine levels. However, sometimes there are not enough PAH genes, which leads to high levels of phenylalanine. The PAH gene converts phenylalanine-4-hydroxylase, the protein associated with phenylketonuria, into tyrosine.
PKU was first discovered in 1934 by Dr. Asbjørn Følling in Norway. Two mentally retarded children were examined by Dr. Asbjørn Følling, which was when he noticed that they excreted phenylpyruvic acid in their urine. Following further observations of his patients, Dr. Asbjørn Følling determined a name and reasoning to the disease PKU. The reasoning is that it was an autosomal recessive genetic disease most likely caused by a block in phenylalanine metabolism.
PKU affects about 13,000 people in the US and approximately 50,000 people worldwide. PKU most commonly affects people of European or Native American ancestry. People with African, Hispanic, or Asian ancestry are less common to be affected by PKU.
The symptoms of PKU range from mild to severe. If an infant has a very slight degree of PKU, called mild hyperphenylalaninemia, there may be no problems. Infants born with mild or moderate forms of PKU have the possibility of mild degrees of mental retardation. If an infant has a very slight degree of PKU, called mild hyperphenylalaninemia, there may be no problems. Infants that suffer from severe PKU, called classic PKU, will appear normal for the few months after birth, but mental retardation and behavioral problems will develop if PKU is gone unnoticed or untreated. More symptoms for classic PKU include seizures, developmental delay, autism, eczema, and lighter skin and hair compared to the rest of the family.
PKU is diagnosed through newborn screening testing on a blood sample (heel stick) that is done soon after birth. However, sometimes, if infants do not have newborn screening tests, PKU can show up in older kids with symptoms associated with PKU.
PKU is mostly treated by a special low phenylalanine diet. Other treatments include eating special medical and low-protein foods and taking vitamins and minerals. People diagnosed with PKU must follow this kind of diet for their entire lives. They should avoid foods that contain high levels of phenylalanine, such as fish, milk, wheat, and beans, and eat more foods like vegetables, fruits, cookies and bread.
The prognosis for a patient diagnosed with PKU is the blood test done after birth.
PKU is an autosomal recessive disorder. Each parent of someone who suffers from PKU carries one copy of an altered PAH gene. The person with PKU has two copies of the altered gene, one from each parent. In the image above, we see two parents who each have one normal gene and one altered gene. There are four combinations of these genes. If the child gets one normal gene from each parent, they are unaffected. If the child gets one normal from mom and one altered from dad, or one normal from dad and one altered from mom, they become an unaffected carrier. The last combination is the child getting one altered gene from each parent, which gives the child PKU.
There is tons of research currently being conducted on PKU, including Kuvan, a drug, and injections to treat and cure PKU, effects of Kuvan and those injections, enzyme substitutions, gene and cell therapy, and transplants.