Symptoms of high or unstable blood Phe levels include:. Going to a clinic will help you learn about options to help you manage PKU. Your care team can help you identify symptoms of high or unstable blood Phe levels, and they can help you determine if what you are experiencing is PKU-related.
Having an honest conversation with a PKU care team can help create a management plan that works within your everyday life. The symptoms of high or unstable blood Phe levels can be hard to recognize. Symptoms of high or unstable blood Phe levels include: Behavioral or social problems Problems with memory "Fogginess," or a slowed processing of information Inattention. Difficulty in decision making, problem solving, and planning Depression Anxiety Irritability.
PKU is an autosomal recessive disease. All offspring of a PKU patient will carry one of the mutations that the affected progenitor has. Therefore, all offspring will be at least carriers of the disease. Whether they will also suffer from the disease or not and with what severity depends on the conditions of the other progenitor and the kind of mutations they both carry. If he or she has no mutations in the PAH gene, all children will be carriers but non will be affected.
If the second parent is a PKU patient as well, then all their offspring will be affected. PKU mothers have a higher frequency of microcephalic and mentally retarded children, even when the child is unaffected by PAH deficiency. Other congenital abnormalities these children suffer include cardiovascular and urinary system malformations, and a higher frequency of miscarriages has been reported.
It has been proven that the frequency of these malformations is in relation with the blood Phe levels the mother has during pregnancy.
Phe acts as a toxic agent for the fetus, similar to alcohol or certain medications. Therefore, PKU women require a stricter treatment during pregnancy. In some areas, screening programs have been developed in order to detect women with mild forms of the disease that might not have been screened before and are at risk of having mentally retarded children. Phenylalanine and other large-neutral amino acids LNAA including valine, leucine, isoleucine, tyrosine and tryptophan use the same transport system across the blood—brain barrier BBB.
Depending on the concentration of these amino acids in the blood there is a competition at the BBB. This has consequences in several biological processes in the brain including synthesis of neurotransmitters, protein synthesis, myelin formation, ultimately leading to the neurological features of PKU.
BH4 is produced in the body and its concentration regulates the conversion of phenylalanine to tyrosine, mainly in the liver. In the brain BH4 is a cofactor of enzymes responsible for the synthesis of the important neurotransmitters catecholamines and serotonin. In some patients with PKU, BH4 can restore residual enzyme activity and promote phenylalanine degradation.
Some PKU patients can completely replace low-phenylalanine diet with the pharmacological therapy with BH4 sapropterin and some need a combination of both therapies. As a cofactor, BH4 binds to the enzyme phenylalanine hydroxylase PAH and together with phenylalanine keeps the enzyme in the active state.
PAH is a homotetramer composed of four identical subunits and BH4 can also act as a chemical chaperone. Pharmacological chaperones are small molecules e. BH4 which stabilize the correct folding of a protein resulting in a recovery of function lost due to mutation and can be used for medical treatment. No, but both diseases present with elevated blood phenylalanine levels. In addition BH4 -deficient patients present with deficiency of catecholamines and serotonin in the brain.
BH4 deficiency is considered to be a more severe disease than PKU and cannot be treated with a low-phenylalanine diet alone. Instead, a substitution with BH4 sapropterin and neurotransmitter precursors is essential. It is therefore essential to diagnose these patients as early as possible, in order to prevent irreversible brain damage.
BH4 deficiency is a group of heterogeneous disorders with several enzymes being affected, and all of them can be detected through the newborn screening for PKU. However, with the known genotype patients can be characterized more precisely and treatment can be adequately tailored. This is particularly useful in view of potential treatment with pharmacological doses of BH4 sapropterin. There is no straightforward answer. Knowing the huge association between brain function and blood phenylalanine, measurement of blood phenylalanine is crucial.
The frequency is related to aspects such as growth, infections, compliance with the treatment and other factors. Apart from this, we know that blood phenylalanine concentrations are related to brain function especially at a young age, and for that reason the frequency at that stage needs to be high.
Some experienced centres advise a frequency of once a week to once every two weeks until two years of age, and then only slightly decreasing the number of measurements to once monthly in adulthood.
It should however be taken into account that at certain times there may be reasons to increase rather than decrease the number of samples. Such reasons include not only illness, but also change of school, change in responsibility, transferring the responsibility from the parents to the patients, leaving maternal home, going from school to university or other school programs for adults, starting the labour process.
The most important method for decreasing the phenylalanine concentration is to decrease the intake of natural protein whatever the cause of the high phenylalanine concentration is. However, there are three factors that should be taken into account: i the possibility of catabolism due to insufficient intake of phenylalanine, ii insufficient intake of other amino acids and iii insufficient intake of energy.
Regarding the first issue, it is of note that, notwithstanding the fact that it is important to prevent too high intake of phenylalalanine, if the intake is too low this can also result in high blood phenylalanine concentrations.
With regard to the second issue, it is important to note that the dietary treatment of PKU consists of a phenylalanine-restricted diet. This means that the total protein intake should be normal, by giving a diet largely restricting the natural protein intake and at the same time guaranteeing a sufficient amount of the amino acids other than phenylalanine that are necessary for the protein synthesis. The third issue is an adequate intake of energy, which means that patients — especially young ones — sometimes need more energy than the healthy population to guarantee the use of protein in the right way.
In healthy individuals phenylalanine is used to build protein and to convert into tyrosine. Conversion into tyrosine is the most important part of the metabolism of phenylalanine, but the precise amount which is converted is unknown and may differ within patients. A theoretical consideration may start with the assumption that almost all phenylalanine is converted into tyrosine in healthy persons. Taking that as a fact, the amount of tyrosine in the amino acid supplement should be the amount of phenylalanine not taken and the normal amount of tyrosine.
That more or less doubles the normal amount of tyrosine. However, this seems too much when aiming at normal concentrations of tyrosine in the blood. There are a few papers showing the importance of tyrosine concentrations and the phenylalanine-to-tyrosine ratio.
However, due to the fact that tyrosine has become an essential amino acid and the large amount of tyrosine in the protein substitutes, the tyrosine concentrations in blood change largely within the time before and after a snack, or other food intake, especially when protein substitute is taken as well. Therefore, it is of importance to measure tyrosine in the overnight fasting state to have a realistic idea about the tyrosine concentrations.
Phenylalanine is one of the so-called large neutral amino acids LNAA. Together these LNAA are transported across the blood—brain barrier into the brain in a competitive way, so that high blood concentrations of one amino acid will have two consequences: the amino acid that is high in the blood will be high in the brain, especially when the transport system has a high affinity to that particular amino acid; the other amino acids will have low concentrations in the brain due to the fact that the large transport of the one specific amino acid high in blood interferes with the transport of the other amino acid.
From the experience with Diabetes mellitus it has been known for a long time that direct knowledge about dietary changes positively influences adherence.
However, real-time home measurement is not available yet in PKU. At present, it is home sampling rather than home measurement. In itself, that is a large improvement compared to the old days when patients very often came to the clinic solely to provide a blood sample for amino acid analysis. With blood sampling at home, there are many clinics that give the results to the patients without advice, thus teaching the patients to be responsible for adjustments themselves.
This has been shown to be possible. However, at the same time, there is more than one reason why the blood phenylalanine concentration does not decrease that much using home blood sampling and making patients responsible for adjusting their treatment.
First of all, patients seem to keep the upper limit of the advised target as the target phenylalanine concentration. Secondly, the frequency of blood sampling has increased tremendously. Where, in the past, patients came to the clinic once every three months, they now get a phenylalanine concentration every 2—4 weeks without the possibility only to adhere to the diet for the week before the blood sampling.
New developments are underway and hopefully real-time home measurement is really possible in the near future. Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. This content does not have an English version. This content does not have an Arabic version.
Overview Phenylketonuria fen-ul-key-toe-NU-ree-uh , also called PKU, is a rare inherited disorder that causes an amino acid called phenylalanine to build up in the body. Email address. First Name let us know your preferred name. Last Name. Thank you for subscribing Your in-depth digestive health guide will be in your inbox shortly. Sorry something went wrong with your subscription Please, try again in a couple of minutes Retry.
Request an Appointment at Mayo Clinic. Autosomal recessive inheritance pattern Open pop-up dialog box Close. Autosomal recessive inheritance pattern To have an autosomal recessive disorder, you inherit two mutated genes, one from each parent. Share on: Facebook Twitter. Show references National Library of Medicine. Genetics Home Reference.
Accessed Oct. National Organization for Rare Disorders. Learning about phenylketonuria PKU. National Human Genome Research Institute. Phenylketonuria PKU. Merck Manual Professional Version. Bodamer OA.
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