Genetics Northern California

Fatty Acid Oxidation Disorders

There are many different types of fatty acid oxidation disorders (FODs), but they all have a similar cause: the body has difficulty breaking down (metabolizing) fatty acids. This leads to at least two serious problems. The most urgent problem is that, without fatty acids, the body runs out of energy and cannot continue to function. The longer-term problem is that the fatty acids that cannot be broken down build up in the body causing damage to the liver and heart. If left untreated, FODs can result in severe muscle cramps, lethargy, confusion, difficulty breathing, seizures, and even death.

Everyone needs fat for energy, growth and vitamin metabolism, but the body cannot use the fat in food until it is broken down (metabolized) into smaller parts. These smaller parts of fat are called fatty acids which, in turn, are broken down into even smaller parts to be used for energy. Although we also get energy from sugars, this type of energy does not last very long. For long-term energy, the body relies on fat, making fat a very important source of energy. In order to turn fat into energy it must go through a process called the beta oxidation cycle. The beta oxidation cycle is a complex process that uses many different enzymes. If any of these enzymes are missing or malfunctioning, the beta oxidation cycle does not work properly and the fatty acids cannot be broken down into energy. For someone with an FOD, "running out of energy" does not mean simply feeling tired. It is a serious medical emergency that must receive prompt treatment.

FODs can vary greatly. Some children die early in infancy before they are ever diagnosed, whereas others are not diagnosed until adulthood. These differences are usually related to the amount of enzyme activity there is to help the beta oxidation cycle break down fat. In some cases the enzyme is missing entirely, and in others the enzyme may be partially functioning.

Types
There are many types of fatty acid oxidation disorders (FODs). The most common types of FODs include:

  • Medium chain acyl CoA dehydrogenase deficiency (MCADD)

  • Long chain acyl CoA dehydrogenase deficiency (LCHADD)

  • Very long chain acyl CoA dehydrogenase deficiency (VLCHADD)

Causes
Fatty acid oxidation disorders are genetic conditions that are inherited. The way they are inherited is called autosomal recessive

Diagnosis
Infants, children and even adults with symptoms suggesting a fatty acid oxidation disorder can be tested with a blood or urine sample. If FOD-type abnormalities are found, further testing will be needed. Diagnosis is confirmed by measuring the amount and type of enzyme activity. Through early detection and prompt treatment, many serious effects of FODs can be prevented. Many forms of fatty acid oxidation disorders are first identified by newborn screening.

Treatment/Services
The goal of FOD treatment is to get enough food and avoid fasting, while not allowing the fat levels to build up. The treatment itself consists of four main parts: diet, formula, supplements, monitoring.

  1. Diet
    Please keep in mind that when we refer to "eating" that this includes any eating, drinking, swallowing, and chewing. When we refer to "foods", this includes all foods, drinks, medications, and even gum.

    The first aim in dietary treatment is to avoid fasting. This means that people with FODs must be careful not to go too long without eating. If they do not eat often enough, their bodies run out of energy. This does not simply mean the person feels more tired than usual; the results are much more serious, including muscle cramping/weakness, disorientation, seizures, coma, and even death. As a result, people with FODs must plan frequent meals and adjust the amount they eat when they are sick or physically active. At these times the body needs more energy than usual. How much depends on how strenuous the activity is, how long it lasts, and what the weather (and altitude) is like. One clue that you will need to eat more is if the activity causes you to sweat. Before such activities it is important to eat a high-carbohydrate snack and then stop for re-fueling if the activity continues. It is best to discuss these special situations with a metabolic dietitian for some guidance as to the optimum type and amount of food given your particular circumstances.

    It is also important to discuss what types of activities you would like to participate in with your doctor in order to determine safe limits for exercise. Some people with FODs simply cannot tolerate too much exercise. They may want to join in the fun, but can easily over-extend themselves without realizing it until they "crash" and end up in the hospital.

    While getting enough food for energy is the biggest concern for people with FODs, it is also important to cut down on the amount of fat in the diet. This means that people with FODs must learn what types of foods are highest in fat and limit these foods. Some examples of foods high in fat include whole fat dairy products, fried foods, pastries, and chips.

    People with FODs must also learn what foods have some amount of fat and ways to find out how much. Each individual, depending on the severity of their disorder, is given a daily limit of fat they can eat. It is okay for people with FODs to eat some fat because, unlike an allergy, the fat will not cause them to have an "allergic" reaction. In fact, people with FODs must eat some fat every day, because everyone needs a certain amount for energy, growth, and vitamin absorption. The trick is not to eat too much. This is done by learning to count and keep track of the amount of fat eaten throughout the day.

    Since dietary fat is limited, people with FODs must get extra energy in the form of carbohydrates. The problem is that many carbohydrate-rich foods are made up of simple carbohydrates. Simple carbohydrates do not provide lasting energy. The body quickly metabolizes them, releasing the energy all at once, so the person's energy level quickly rises then drops. In order to get a longer-lasting, steady stream of energy, the person must eat food with complex carbohydrates. One of the best sources of complex carbohydrates is cornstarch. Cornstarch breaks down slowly, so it releases a steady amount of carbohydrates over several hours. This provides a more consistent and reliable source of energy for the body.

    One of the main problems in following an FOD diet is balance. How much food is needed and how often? Too little food is dangerous, but too much can lead to obesity which causes other problems over time. How much extra should be eaten for different levels of exercise? How much of the food can be fat and how much should be carbohydrate? What kind of fats/carbohydrates are the best? The solution: regular consultation with one of the Regional Metabolic Clinic dietitians.

  2. Formula
    The second part of the treatment for some people with FODs is drinking a special formula. This formula helps supply the fat missing from the diet in a form that the body can absorb. For instance, formulas made with MCT oil (medium-chain triglycerides/fat) provide a source of fat (energy) that people with long-chain deficiencies (e.g., LCHADD or VLCHADD) can more easily use. MCT oil as part of a formula or taken separately as a supplement is an important part of treatment for the long-chain disorders.

    However, MCT oil would be one of the worst things for people with medium or short-chain deficiencies. For these disorders there is no set formula, unless you include cornstarch as a "formula". The best treatment for medium and short-chain disorders, as for all FODs, is simply to eat frequent meals.

  3. Supplements/Medications
    MCT (Medium Chain Triglicerides) Oil: Sometimes this oil is used on its own as a supplement when the formula with MCT does not provide enough or the person cannot tolerate the formula for other reasons.

    Carnitine: Carnitine supplementation is an important part of the treatment in FODs because it helps the body get rid of some of the toxic acid byproducts from fat metabolism. The carnitine is able to bind to these toxic acids and carry them out in the urine.

  4. Monitoring
    The final part of the treatment for FODs is monitoring. Monitoring helps makes sure the other three parts of the treatment (diet, formula, supplements) are keeping the levels of toxic fatty acids low, while still maintaining normal levels of usable fat and carbohydrates for energy. It is important to find out if the treatment is working in order to avoid medical problems. 

    Blood testing - Monitoring is done by regularly measuring some or all of the following: acylcarnitine, carnitine, ammonia, CK (muscle function test) and AST/ALT (liver function tests). The blood samples are taken at the hospital lab and sent down to the Metabolic Laboratory at Kaiser in Los Angeles for testing. It can take several days to a week to receive the results. Please note: not all these tests are done with every set of labs.

    Urine testing - Monitoring is also done by testing the level of organic acids and acylglycine in the urine. Both these tests (Urine Organic Acids and Urine Acylglycine) require a urine sample that must be frozen immediately. The urine for organic acids is sent down to the metabolic lab at Kaiser, South in Los Angeles. It can take several days to a week to receive the results. The urine for acylglycine testing is sent out to Yale University School of Medicine in New Haven, CT. For this reason, samples must be collected early in the week (M-W) and results can take up to 2 weeks to come back.

    à Please Note: For all blood and urine tests, a 3-day diet record is recommended. Testing is done on the 4th day, right after the diet record is completed. The diet record is an important part of interpreting the test results. It is hard to get an accurate picture of what is happening inside the body without having the information provided by the diet record.

Reference Books

The Complete IEP Guide 
Publisher:  Nolo Press
This book explains every nuance of the IEP process in lay terms. It provides clear concise explanations, definitions, and descriptions backed by legal codes (code reference numbers are included after every section). It also includes practical suggestions on how to deal with any problems that may arise. Sixth edition published February 2009.

How to Teach Nutrition to Kids
by Connie Liakos Evers, MS, RD
Published by 24 Carrot Press, Tigard, OR, 1995
Third edition published April 2006.

Positive Discipline
By Jane Nelson, EdD
Published by Ballintine Books, New York, NY

Positive Discipline for Teenagers
By Jane Nelson, EdD, and Lynn Lott, MA
Published by Prima Publishing, Roseville, CA, 2000

Social Security Disability: Getting & Keeping Your Benefits
Publisher: Nolo Press
A legal guidebook to navigating the Social Security system written in plain-English. Helps the layperson to understand Supplemental Security Income (SSI) and Social Security Disability Insurance (SSDI) and the laws behind them (includes legal reference codes after each section). Forth edition published March 2008.

We're Different, We're the Same
by Bobbi J. Kates. Illustrated by Joe Mathieu.
Published in 1992 by Random House. Suggested ages: 4-8
Sesame Street characters learn to appreciate their differences and discover that they still have many things in common.

Why Can't I Eat That!: Helping Kids Obey Medical Diets
By John F. Taylor, PhD, and R. Sharon Latta
Published by R & E Publishers, Saratoga, CA, 1987