Propionic acidemia (PPA) is a condition that occurs when the body is missing an enzyme needed to break down protein. When this enzyme is missing, parts of the protein build up in the body and cause damage to the nervous system, especially the brain. If left untreated, PPA can result in vomiting, anorexia, cardiac problems, blood disorders, failure to thrive, develomental delays, mental retardation, and even death.
Everyone needs protein for growth and repair of body tissues, but the body cannot use the protein in food until it is broken down into smaller parts. These "smaller parts" of protein are called amino acids. In PPA, four of these amino acids cannot be broken down. These four amino acids are called:
They should be broken down by an enzyme called propionyl-CoA carboxylase (PCC). In people with PPA the PCC enzyme is either missing or does not work well. As a result, these amino acids cannot be broken down properly, causing propionic acid (PPA) to build up in the blood and damage the body, especially the brain.
People with PPA also have trouble completely breaking down fat. Like protein, fat is broken down into smaller parts the body can use, called fatty acids. Certain fatty acids are not broken down in a person with PPA. These include some of the odd-chain fatty acids and polyunsaturated fatty acids.
PPA is caused by a change (mutation) in a specific gene and is an inherited disorder. The mode of inheritance is called autosomal recessive, meaning that each parent carries a gene for the disorder that is passed on to the baby. A person with the disorder has two copies of the altered gene: one from the mother and one from the father.
Infants, children and even adults that exhibit symptoms of PPA can be identified with a simple blood test that measures the amount of PPA in the blood. Further testing measuring the amount and type of enzyme activity is done to confirm the diagnosis. Through early detection and prompt treatment, many serious effects of PPA can be prevented.
The goal of PPA treatment is to keep the level of PPA in the blood as low as possible in order to avoid any of the poor consequences of having high levels. The treatment itself consists of four main parts: diet, formula, supplements, monitoring.
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 treatment is to cut down on the amount of protein that the person eats. This means that people with PPA must learn what types of foods are highest in protein and limit these foods. Some examples of foods high in protein include all types of meat (e.g., chicken, pork, beef, seafood), all types of dairy (e.g., milk, yogurt, cheese, whipped cream, ice cream, etc.), all types of beans and nuts (e.g., soybeans, pinto beans, peanuts, etc.), and eggs.
People with PPA must also learn what foods have protein and ways to measure how much. Each individual, depending on the severity of their disorder, is given a daily limit of the protein they can eat. It is okay for people with PPA to eat some protein because, unlike an allergy, the protein will not cause them to have an allergic reaction. In fact, people with PPA must eat some protein every day as everyone needs some isoleucine, methionine, threonine, and valine for growth and development. The trick is not to eat too much. This is done by learning to count and keep track of the amount they consume throughout the day.
One of the main problems in following the PPA diet is nutritional balance. Foods that are low in protein tend to be high in either fat or sugar or both. While some low-protein foods can be very nutritious, such as low-protein vegetables and fruit, others offer mostly "empty" calories. Foods that are high in empty calories supply a person with calories, but little nutrition. These calories are often needed for energy and growth but, when consumed in large amounts, can lead to obesity.
Another problem is creating enough variety in the diet, especially for picky eaters. One way to increase variety is to eat low-protein specialty products. For instance, instead of avoiding all breads, pastas, and rice (which often have too much protein), people with PPA can try some of the special low-protein versions of these foods. There are also many other types of low protein foods available, such as cheese, peanut butter, pizza, etc. As of July 2000, California State law (Senate Bill #148) requires all health insurance companies to provide low-protein specialty foods free of charge to all patients with a condition called PKU. Kaiser Permanente has expanded this requirement to include patients with any metabolic condition requiring a low-protein diet. The Regional Metabolic Clinic has contracted with several different specialty food companies to provide these products. In order not to be charged for these products, patients must fill out RMC order forms and return them to the clinic for review and approval. The coordinators will then forward these forms on to the company(ies) and the food will be delivered directly to the patient's home. Limit: $2500 per patient per year.
Formula: The second part of the treatment for PPA requires a special protein formula. PPA formulas are special because they contain all the amino acids a person needs, but is limited in isoleucine, methionine, threonine, and valine. It is almost impossible to get enough protein to stay healthy on a PPA diet alone. Therefore, people with PPA need to drink formula in order to get enough protein without too much of the amino acids they need to avoid. The formulas are fortified with essential vitamins and minerals. Fortunately, today there are several different PPA formulas to choose from.
Biotin - Some forms of PPA can be treated with high doses of one of the B-vitamins: biotin. This vitamin is a co-factor that helps the propionyl-CoA carboxylase (PCC) work better. Whether or not a patient has the biotin-responsive form of PPA determined early in the treatment process. If the patient does not have this form of PPA no amount of biotin will help. We strongly advise against self-treatment as it may cause unwanted side-effects or interfere with other treatments.
Carnitine - Another supplement used to lower PPA levels is a medication called carnitine. Carnitine is an important part of the treatment in PPA because it helps the body get rid of some of the toxic acid byproducts by binding to them and carrying them out in the urine.
Isoleucine - Due to the protein restriction of the diet, some people with PPA develop a deficiency of isoleucine (one of the essential amino acids). When this happens, isoleucine supplementation is recommended to correct the deficiency.
Valine - Due to the protein restriction of the diet, some people with PPA develop a deficiency of valine (another one of the essential amino acids). When this happens, valine supplementation is recommended to correct the deficiency.
Monitoring: The final part of the treatment for PPA is monitoring. Monitoring is done in order to know whether the treatment (diet, formula, supplements) is working to keep the level of PPA as low as possible as well as maintain normal levels of isoleucine, methionine, threonine, and valine. It is best to find this out before the person with PPA experiences any of the possible bad effects. Monitoring is done by testing the levels of PPA as well as all the amino acids in the blood on a regular basis. The blood samples are drawn through a needle 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.
Other tests for monitoring PPA can include:
Carnitine level: to see if dose needs adjusting
Electrolytes (sodium, potassium, chloride, carbon dioxide): checks balance of pH in the blood.
BUN/Creatinine: tests for kidney function
CBC: tests for anemia
Albumin: tests whether the person is getting enough protein for growth and tissue repair
Urine Ketones: an early sign that toxic acids are building up in the body
*Note: Not all of these tests are done with every set of labs.
For all blood tests, a 3-day diet record is recommended. To complete a diet record all the food eaten over the period of three days must be written down along with the amount eaten. The blood test(s) should be taken on the 4th day, right after the diet record is completed. The diet record is an important part of interpreting the test results. For instance, if the PPA level is high, is it because the person is eating too much protein or too little? It is hard to get an accurate picture of what is happening inside the body without having the information provided by the diet record.
Patients are regularly weighed and measured at clinic and regular doctor visits in order to monitor their growth and development. School reports can also help identify any learning disabilities.
Low Protein Cookery for PKU (Please note: this book is helpful for all low-pro diets.)
by Virginia Schuett
Published by the University of Wisconsin Press, Madison, WN, 1997
Available through Kaiser's Regional Metabolic Clinic
The Complete IEP Guide published by 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.
How to Teach Nutrition to Kids
by Connie Liakos Evers, MS, RD
Published by 24 Carrot Press, Tigard, OR, 1995
By Jane Nelson, EdD
Published by Ballantine Books, New York, NY
Positive Discipline: The First Three Years
By Jane Nelson, EdD
Published by Ballantine Books, New York, NY
Positive Discipline for PreSchoolers
By Jane Nelsen, EdD, Cheryl Erwin, & Roslyn Duffy
Positive Discipline for Teenagers
By Jane Nelson, EdD, and Lynn Lott, MA
Published by Prima Publishing, Roseville, CA, 2000
Positive Time Out and 50 Other Ways to Avoid Power Struggles in Homes and Classrooms
By Jane Nelsen, EdD
Social Security Disability: Getting & Keeping Your Benefits published by 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).
Temperament Tools: Working with Your Child’s Inborn Traits
By Helen Neville and Diane Clark Johnson
Published by Parenting Press, Inc., Seattle, WA, 1998
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