School of Medicine

Department of Genetics

Dietary Treatment For Metabolic Disease

Amy Cunningham, MS, LDN, RD

Metabolism is the word which describes how the body breaks down the nutrients found in food and uses them for energy, growth, healing, and all other body functions. An "inborn error of metabolism", or metabolic disease, occurs when a person inherits abnormal (mutated) genes that stop or change the flow of normal metabolism. There are hundreds of metabolic diseases that vary widely in severity and rarity. In many of these diseases diet is the primary - and often the only - treatment.

The Basics
In order to grow, a child has to obtain enough protein and calories from the food he eats to build a body that is continually stretching and maturing; and an adult needs protein and calories to keep the body working and in good repair. The protein that makes up all the body's cells and tissues, as well as the protein in the food we eat consists of individual building blocks called amino acids. These amino acids are linked together into long protein chains. When food protein is digested, the chains are split apart into individual amino acids. These are absorbed and then put together again in different combinations to make protein structures the body needs. When more food protein is eaten than is needed to make body protein, excess amino acids are either burned as fuel for energy, or changed into other compounds.

None of this can happen without the help of small body proteins known as enzymes. Each time one compound is changed into another at one of thousands of steps along the body's intricate series of metabolic pathways, an enzyme is needed to make it happen. Each enzyme is made by a specific gene. When that gene is abnormal, it's enzyme isn't made properly and the chemical pathway dependent on that enzyme is blocked. Like a river that is damned, the compounds flowing into the pathway can't be processed, so they accumulate and may become very harmful. Also, on the "downstream" side of the pathway, the normal product isn't made. Often the result is metabolic disease.

The Theory
Diets used to treat metabolic diseases vary with the specific disorder, but the principles are the same. Food providing the substance that accumulates at the blocked pathway is restricted so that harmful amounts won't build up. This substance may be a sugar, or a fat, but it is most often particular amino acids found in protein. In theory this seems very easy, but translating theory into food on the table is often very complicated. Using the treatment for one metabolic disease as an example can make it easier to understand.

An Example - PKU
The most common metabolic disease, and the first one to be treated by diet, is Phenylketonuria, or PKU. Before the 1960's, untreated PKU was one of the most common causes of mental retardation in the United States. Now all newborns in the US are given a blood test at birth that can diagnose PKU. If dietary treatment is begun early, and continued throughout life, children with PKU can expect to reach adulthood with normal health and intelligence. In earlier years it was believed that dietary treatment could be stopped at the age when brain growth was complete. However it is now known that children and adults who stop following dietary restrictions can experience learning disabilities, hyperactivity, shortened attention span, and other problems. For this reason, the PKU diet - and any other metabolic diet - is considered to be a lifelong treatment.

In PKU, not enough of the enzyme phenylalanine hydroxylase can be made. This enzyme is part of a metabolic pathway that changes one amino acid (phenylalanine) into another (tyrosine). The pathway is used when more food protein, containing phenylalanine, is eaten than is needed for building body protein. If there is no enzyme available, the pathway is blocked. Phenylalanine accumulates in the blood in amounts that are toxic to the brain; and tyrosine, which is also needed for healthy brain function, cannot be made.

Treatment for PKU
Dietary treatment of PKU begins with limiting the amount of phenylalanine going into the blocked pathway. Because the amount of protein found in a normal diet contains much more phenylalanine than can be tolerated by a person with PKU, foods containing protein must be severely limited.

However, phenylalanine cannot be totally taken out of the diet. There are about twenty different amino acids needed by the body. The body can make some of these for itself, usually from other amino acids, but some must be obtained from food. These are called "essential amino acids", and phenylalanine is one of them. Because the body won't build an incomplete protein, if an amino acid needed to make a protein isn't there, or can't be made (as essential amino acids can't be), the protein won't be built. It would be similar to trying to write a sentence with all the vowels removed from the alphabet.

A certain amount of phenylalanine is essential. If the diet doesn't provide enough, the body will break down muscle protein to obtain it. In a person with PKU, this will release as much phenylalanine into the blood as eating a hamburger would.

The PKU Diet
The PKU diet is based on providing enough phenylalanine to build body protein and provide for growth in children, but not so much that the blocked pathway is used beyond it's capabilities. Not too much - and yet not too little. In addition, tyrosine must be added to replace that which can't be made by the blocked pathway.

However, if a diet is restricted to the amount of food that provides the very small amount of phenylalanine that can be tolerated, the body will not have enough protein or calories to support growth or good health. A special metabolic formula must also be included in the diet. These formulas are processed to remove phenylalanine, supplement tyrosine, and provide a source of additional calories and protein that can be tolerated. Similar formulas are available for the specific needs of other metabolic diseases.

Because one person's nutritional needs are different than another's, and because everyone's needs change as they grow and mature - a PKU diet must be adjusted often to the individual needs of each person, at each stage of their life. Good dietary treatment of PKU means maintaining that perfect balance of phenylalanine, protein, and calories that supports normal growth and health, but doesn't cause harm.

Translating a Diet Prescription into Food on the Table
For babies, following a PKU diet prescription is easy. The proper amount of phenylalanine is provided by normal baby formula. The addition of phenylalanine-free metabolic formula provides the rest of what is needed for growth.

When a child begins to eat solid food, the regular infant formula is gradually replaced by foods containing the same amount of phenylalanine. The metabolic formula will remain a lifelong part of the diet, and will always have to be relied on as a major source of calories and protein.

High protein foods (such as fish, chicken, eggs, milk, cheese, dried beans, nuts, and tofu) cannot be eaten. The amount of phenylalanine in a one serving of meat is more than can be tolerated by most children in a whole day. Foods containing smaller amounts of protein, such as breads and starches are also often too high to be included, and even the amount of protein in fruit and vegetables must be counted.

Foods must be chosen only from special lists, weighed or measured accurately, and milligrams of phenylalanine counted daily. By the end of a day the total amount of phenylalanine eaten should be no more or less than what is in the diet prescription.

The quantity and variety of food in a PKU diet can be greatly increased by using special low protein food products. For example, a slice of bread or serving of pasta will contain 200 or more milligrams of phenylalanine, while a comparable serving of low protein products will contribute only 15 to 20 milligrams. In a typical diet prescription of as little as 300 milligrams phenylalanine a day, these foods are essential.

Monitoring Control
The success of treatment can be monitored by regularly measuring phenylalanine levels in the blood. If plasma levels fall within a recommended treatment range (2-8 mg%) the brain is thought to be protected from the toxic effects of phenylalanine. It is important to monitor blood levels frequently, especially in a rapidly growing child, so that dietary changes can be made as often as they are needed. Regular clinic visits are also important so that growth and development can be measured.

Compliance and Barriers to Success
Compliance with the restrictions of metabolic diets is often a struggle. The diet is complicated. It requires careful measurement, calculation, and record keeping. It requires buying and preparing foods that are different from what the rest of the family eats, as well as more planning time and more food preparation time. Low protein specialty foods that make the diet more "normal" are very expensive, and are not commonly available in retail stores. The metabolic formula has a very strong taste, and may not be accepted well. It is also important to note that in metabolic diseases other than PKU, the consequences of poor dietary compliance can be life threatening.

Trying to enforce diet restrictions with a young child who is reaching for independence makes a perfect opportunity for power struggles with parents. Allowances for the child's emerging individual taste preferences, developmental stages, and behavior patterns must be made, while at the same time managing a very complicated diet.

Older children and teenagers face still other challenges. Trying to follow a very restricted diet in a lifestyle that includes school cafeterias, vending machines, and fast food restaurants is very hard to do - and fear of being "different" can encourage cheating.

Young people stop following their diets most often because of these psychological issues. High blood phenylalanine, which results from poor compliance with dietary restrictions, can affect a person's ability to concentrate and make good decisions. When poor decisions are made, compliance gets even worse, and the cycle repeats.

Overcoming these barriers to good treatment requires long term commitment by the whole family. A parent must accept the importance of dietary treatment, learn to manage it, and then be able to teach their child the skills needed to assume responsibility for their own treatment as they grow up.

Dietary treatment is successful for many metabolic diseases that could not be treated even 10 years ago, and can make it possible for people with metabolic disease to live normal, healthy lives. However, success depends on compliance with significant restrictions that are complicated and often difficult to follow. New products that make these diets easier to live with are continually introduced, and research is ongoing to find new therapies. For now, diet is the medical treatment, and should be followed with care throughout life.

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