Amino acids include tyrosine (Tyr), phenylalanine (Phe), tryptophan, threonine, methionine, valine, isoleucine, leucine, and histidine. For people unaffected by PKU, all amino acids except Tyr are essential amino acids. For people with PKU, Tyr becomes an essential amino acid. A person must consume essential amino acids to maintain their health.
Blood-brain barrier (BBB) is a selective barrier than prevents some microscopic particles from entering the brain through the bloodstream.
Bone mineral density (BMD) refers to the amount of minerals that are in the bones. A BMD test measures the density of a person’s bones using an X-ray or a computed tomography (CT) scan (a series of X-rays taken from different angles while the person lies on a table). A person with low bone density is at an increased risk of fractures.
Enzyme substitution involves using an alternate enzyme, phenylalanine ammonia lyase (PAL), which is found in plants and bacteria and can break down Phe. On its own, PAL is destroyed very quickly in the body. To work, a protector (PEG), or “coater,” needs to be placed around PAL to slow the speed at which it breaks down in the body and to protect it from the body’s immune response. The result is PEG-PAL, an injectable medicine that has been shown to lower Phe levels in mice with PKU. The first study of PEG-PAL in human patients with PKU began in 2008, with the aim to show a decrease in Phe levels in PKU patients. Successful Phase 1 results were reported in June 2009.
Executive functioning refers to high-level abilities that influence processes such as attention, memory, and motor skills. Executive function (EF) allows a person to successfully engage in independent, purposeful behaviors. For a person with PKU, elevated Phe levels may result in difficulties with EF such as having problems with planning, carrying out a task or assessing the progress being made during a task.”
Food nutritional labels: The method of counting grams of protein is generally used by people with a higher Phe and protein tolerance. A “Nutrition Facts” label is required for most packaged foods in the US. For people with PKU, the most important nutrition facts listed are serving size (by grams or pieces) and protein (grams) based on the serving size listed. Before eating any packaged food, check the Nutrition Facts label to see how much protein is in each serving, and weigh or count out your serving to make sure that you are only eating the amount of protein you have planned for that snack or meal. While this may not be the most accurate way to keep track of the amount of Phe you consume, counting grams of protein might be the easiest way for you to become accustomed to a low-protein diet. Be aware that Nutrition Facts labels aren’t always exact. Due to the food labeling laws, items that say, “Protein 0g” may actually contain up to 0.49 g of protein per serving. If a label says that one serving of a given food item has 1 gram of protein, it can contain 0.5 to 1.49 g of protein. If you do not have a PKU food list or if it is a new product and the label says “Protein 0g”, it is best to assume that it has 0.5 g of protein15. You can also add 0.5 g to any rounded number to come up with the maximum grams of protein in each serving.
A food reference guide shows how much protein and Phe common foods contain, which helps you figure out and plan how much protein and Phe you will consume at each meal or snack. It also lists “free foods” —foods that contain little or no protein, and so do not need to be counted. The dietitian at your PKU clinic may give you a reference guide and help you use it.
Gene therapy would be an ideal treatment for PKU because it would provide functional PAH to the liver cells in order could break down Phe. Unfortunately, the challenge in gene therapy has been the body’s immune response, which mounts an attack on the transferred enzymes as it would with a virus. While gene therapy has worked in curing PKU in mice, immunosuppressant medications have also been needed to maintain the correction. Some new techniques have shown promise as safer, though, causing less immune response and maintaining a longer correction.
Interpersonal sensitivity is a person’s ability to accurately assess the appropriateness of their responses, judgements and interpretations of others.
Kuvan® (sapropterin dihydrochloride) is a FDA-approved pharmaceutical version of tetrahydrobiopterin (BH4),* which naturally occurs in a person’s body, that is used as a treatment method for some patients with PKU. KUVAN works by helping the phenylalanine hydroxylase (PAH) enzyme work more effectively to break down Phe in the body. Not all people with PKU will respond to Kuvan. For people with PKU who respond, Kuvan will help to maintain Phe levels within the recommended treatment range. Many people who respond to Kuvan will be able to modify their diet to allow more natural protein. For more information about Kuvan, visit www.Kuvan.com. * BH4 is the cofactor for the enzyme involved in the metabolism of phenylalanine.
Large neutral amino acids (LNAAs) are amino acids that naturally occur in a person’s body. Tyrosine (Tyr), phenylalanine (Phe), tryptophan, threonine, methionine, valine, isoleucine, leucine, and histidine are all LNAAs. All except Tyr are essential amino acids for people who do not have PKU. For those with PKU, Tyr also becomes an essential amino acid, as increased Phe becomes toxic to the brain. All LNAAs share the same transport to the brain. For people with PKU, the rationale for increasing the intake of LNAAs (without Phe) is that the LNAAs will compete with Phe to be transported to the brain. This reduces the amount of Phe in the brain, and also increases the amount of other LNAAs in the brain. Both of these factors may positively impact the neurocognitive function that people with PKU experience.
For more information about LNAAs, visit ..link..
Measuring using measuring cups or spoons
You will need the cups or spoons and a calculator. This process may be slightly more difficult than measuring by weight.
1. Convert any fractions to decimals. To do this, divide the number on the top of the fraction by the number on the bottom. For example, for ¼, 1 ÷ 4 = 0.25. Or ¾ is 3 ÷ 4 = 0.75.
2. Divide the portion size of the serving you are using by the number you will find in the “Measurement” section of your food reference guide.
3. Multiply this number by the number in “Phe mg” column of your food reference guide. This will give you the amount of Phe in the serving you are using.
Example: You wish to serve ½ cup of a particular cereal, but the cereal is listed using ¾ cup:
1. 1÷2 = 0.5 is your serving. 3÷4 = 0.75 is the serving size listed.
2. Divide your serving by the serving listed. 0.5 ÷ 0.75 = 0.66
3. Multiply 0.66 by the number in the “Phe mg” from the food reference guide. If it is 45 mg Phe, it would be: 0.66 x 45 = 30 mg Phe.
If you are unable to obtain the amount of Phe in a food or beverage, it is possible to estimate how much Phe it contains using the serving size and nutrition information on a food label (see example of a food label below). Commit to memory that 1 gram of protein contains about 50 mg of Phe. If you multiply the number of grams of protein by 50 you can get a rough estimate of how much Phe is contained in that food or beverage12 1 gram of protein = 50 mg Phe For example, if the food has 4 grams of protein, multiply 4 by 50 to get 200 milligrams Phe. 4 g of protein x 50 (number of mg Phe in each g of protein) = 200 mg Phe. Remember, this is only an estimate and is not an exact method to calculate Phe content. Sometimes food manufacturing companies may be able to give you additional nutrition information, or you can call your dietitian to see if they can find more information on a particular food.
The term “medical foods” may include both medical formula as well as foods modified to be low in protein. The foods modified to be low in protein provide an essential energy source and satiety with less than 1 gram of protein. Medical Food Manufactures.
Medical formula provides all of the essential amino acids found in protein (except for Phe), as well as tyrosine, vitamins, minerals, and trace elements that your body needs. Most people who do not have PKU get these from their diet.
Magnetic Resonance Imaging (MRI): A procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. MRI makes better images of organs and soft tissue than other scanning techniques, such as computed tomography (CT) or X-ray. MRI is especially useful for imaging the brain, the spine, the soft tissue of joints and the inside of bones.
Phenylalanine Hydroxylase (PAH): An enzyme that helps change phenylalanine to tyrosine. In PKU, PAH is mutated and possesses less activity than a normal PAH. There are over 500 different known mutations of PAH that can cause PKU, some more severe than others.
Phenylalanine (Phe) tolerance is the amount of Phe a person can consume from natural foods without impacting their metabolic control, or Phe levels.
Phe exchanges: The method of keeping track of Phe intake by counting exchanges and using nutritional labels was developed to help make the process of calculating your intake easier. Phe exchanges are values assigned to a food item for easy reference. Exchanges can be found in most food reference guides and make use of decimals rather than percentages to make calculations easier. Counting exchanges is not as detailed and accurate as counting Phe by milligrams, but counting by exchanges is based on:
1 g protein = 50 mg Phe
1 exchange = 15 mg Phe
1 g protein = 3.5 exchanges
If you're using the same measurements as in the food reference guide, it is easy to just record the number of exchanges listed. If you are not using the same amount, you will need to measure the milligrams of Phe using method 1. For example, if you measure the food and determine Phe = 45 mg, you would divide 45 mg of Phe by 15 (the milligrams of Phe in 1 exchange) to determine that the food you are preparing has three exchanges. If you know that you or your child can have 20 exchanges of Phe per day, that means you or your child can have 300 mg of Phe per day. Rather than counting to 300 every day, you just have to get to 20!
Individuals with PKU must monitor their blood Phe levels to ensure that their levels remain in a healthy range. Blood samples are taken at home and at the PKU clinic to be analyzed. Your food record helps the PKU clinic dietitian adjust your PKU diet appropriately.
Protein is a component of food that is key to supporting growth, but it is also high in phenylalanine (Phe). People with PKU have to restrict protein from natural food sources to maintain control over Phe levels.
Psychiatric symptoms associated with people with PKU, especially those with high Phe levels, include anxiety, depression, and phobias.
Psychoticism involves the ability to control impulsivity, aggression and interpersonal hostility. It has been related to depleted levels of dopamine in the brain.
Tyrosine (Tyr) is an amino acid (AA) that is generally consumed in food. It is essential for several functions, including functions in the brain. For people who do not have PKU, Tyr is not an essential AA as their bodies can change Phe to Tyr, but for people with PKU who are unable to change Phe to Tyr, Tyr becomes an essential AA. Tyr is required for thyroxine, catecholamines, and melanin. People with PKU should have their Tyr levels monitored with their regular blood Phe assessments.
White matter is mostly made up of nerve fibers in your brain that send electrical signals to process information. It is called “white matter” because it appears white, mainly because of a white-colored insulating layer on your nerve fibers called the myelin sheath.