ORGANIC ACID DISORDER
Disorder name: Propionic Acidemia
- What is PA?
- What causes PA?
- If PA is not treated, what problems occur?
- What is the treatment for PA?
- What happens when PA is treated?
- What causes the PCC enzyme to be absent or not working correctly?
- How is PA inherited?
- Is genetic testing available?
- What other testing is available?
- Can you test during a future pregnancy?
- Can other members of the family have PA or be carriers?
- Can other family members be tested?
- How many people have PA?
- Does PA happen more often in a certain ethnic group?
- Does PA go by any other names?
- Where can I find more information?
This fact sheet contains general information about PA. Every child is different and some of these facts may not apply to your child specifically. Certain treatments may be recommended for some children but not others. All children with PA should be followed by a metabolic doctor in addition to their primary care provider.
WHAT IS PA?
PA stands for “propionic acidemia.” It is one type of organic acid disorder. People with PA have problems breaking down and using certain amino acids from the food they eat.
|This is a group of rare inherited conditions. OA disorders are caused by one or more enzymes that do not work properly. People with these conditions cannot digest certain parts of protein from the food they eat. This causes harmful substances to build up in their blood and urine. This can cause serious effects on health, growth, and learning.:
Organic acid disorders (OAs) are a group of rare Acquiring a trait from one’s parents. Most traits, such as eye color or hair color, are inherited from a parent through genes. conditions. They are caused by enzymes that do not work properly. A number of A molecule that helps chemical reactions take place. For example, enzymes in the stomach speed up the process of breaking down food. Each enzyme can participate in many chemical reactions without changing or being used up. are needed to process protein from the food we eat for use by the body. Problems with one or more of these enzymes can cause an organic acid disorder.
People with organic acid disorders cannot break down A molecule that makes up many parts of every cell in the body. Examples of proteins include hormones, enzymes, hair, and antibodies. Proteins are made up of 20 different types of individual units called amino acids. It is the order of these amino acids in a protein that determines what form and function a protein has. Each gene holds the instructions for making a single protein. properly. This causes harmful substances to build up in their blood and urine. These substances can affect health, growth, and learning.
The symptoms and treatment vary between different organic acid disorders. They can also vary from person to person with the same organic acid disorder. See the fact sheets for each specific organic acid disorder.
Organic acid disorders are inherited in an autosomal recessive manner and affect both males and females.
WHAT CAUSES PA?
In order for the body to use protein from the food we eat, it is broken down into smaller parts called Amino acids are small molecules that make up proteins. There are over 100 different amino acids, but our body uses only 20 amino acids to make all of its proteins. Our genes determine the sequence of amino acids in a protein. This sequence determines what shape the protein takes, and what function that protein serves in the body.. Special enzymes then make changes to the amino acids so the body can use them.
PA occurs when the enzyme “propionyl CoA carboxylase” (PCC) is either missing or not working properly. This enzyme’s job is to change certain amino acids so the body can use them. When this enzyme is not working, substances called glycine and This is one type of fatty acid. Large amounts build up in the blood of people with a metabolic disorder called propionic acidemia. If not treated, this condition can cause serious health problems., along with other harmful substances, build up in the blood and cause problems.
The four amino acids that cannot be used correctly are This is one of 20 amino acids that make up protein. It is not made by the body and must be eaten in the diet. It is found in all foods that contain protein., This is one of 20 amino acids that make up protein. It is not made by the body and must be eaten in the diet. It is found in all foods that contain protein., This is one of 20 amino acids that make up protein. It is not made by the body and must be eaten in the diet. It is found in all foods that contain protein., and This is one of 20 amino acids that make up protein. It is not made by the body and must be eaten in the diet. It is found in all foods that contain protein.. These amino acids are found in all foods that contain protein. Large amounts are found in meat, eggs, milk, and other dairy products. Smaller amounts are found in flour, cereal, and some vegetables and fruits.
IF PA IS NOT TREATED, WHAT PROBLEMS OCCUR?
Each child with PA is likely to have somewhat different effects. Many babies with PA start having symptoms in the first few days of life. Others have their first symptoms sometime in infancy. There are also some people who have mild or no symptoms.
PA causes episodes of illness called This is a serious health condition caused by low blood sugar and the build-up of toxic substances in the blood. Symptoms of a metabolic crisis are poor appetite, nausea, vomiting, diarrhea, extreme sleepiness, irritable mood and behavior changes. If not treated, breathing problems, seizures, coma, and sometimes even death can occur.Metabolic crises happen more often in people with certain metabolic disorders (some fatty acid oxidation disorders, amino acid disorders, and organic acid disorders). They are often triggered by things like illness or infection, going without food for a long time, and, in some cases, heavy exercise.. Some of the first symptoms of a metabolic crisis are:
- poor appetite
- irritable mood
- extreme sleepiness or lack of energy
- low In order to hold our posture and control our movements, a certain amount of tension is needed in our muscles. This tension is called “muscle tone.” People with hypotonia have too little tension in their muscles and appear “floppy.” People with hypertonia have too much tension in their muscles and have problems with tight, rigid muscles and joints. (floppy muscles and joints)
- heart problems
Common lab findings are:
- ketones in the urine
- high levels of acidic substances in the blood, called This happens when acidic substances build up in the blood. It can cause rapid breathing, confusion, and extreme sleepiness. If not treated, it may lead to shock, coma or death.
- high blood ammonia levels
- high blood levels of This is one of 20 amino acids that make up protein. It has many functions, one of which is helping cells create energy for the body. It is made by the body and does not need to be eaten in the diet. It is also available as a supplement. People with isovaleric acidemia (IVA) are often given glycine to help prevent health problems.
- high levels of certain These are substances in the cells of the body that help break down fat, sugar and protein from the food we eat. Babies with organic acid disorders often have excess amounts of specific organic acids in their blood and urine. This can cause serious effects on health, growth, and learning.
- low This is a type of blood cell that helps to clot the blood. Platelets help prevent or control bleeding.
- low white blood The smallest living unit. Cells make up all organs and tissues in multi-cellular organisms, like humans. They can also live independently, as in bacteria and other microorganisms. At a minimum, a cell is surrounded by a membrane, contains DNA at some stage in its life, and is able to replicate itself into two equal parts.
If a metabolic crisis is not treated, a child with PA can develop:
- breathing problems
- These are also called "convulsions" or "fits." During a seizure, a person loses consciousness and control of his or her muscles. It may also cause involuntary movements. Seizures can happen for many reasons. Some causes are metabolic disorders, a metabolic crisis, brain injury, and infection.
- swelling of the brain
- This is when the blood or oxygen supply to part of the brain is stopped. It can be caused either by a blood clot or a leak in a blood vessel. A stroke may cause loss of speech and language and the ability to move certain body parts. If severe, it can cause death.
- This is a sleep-like condition from which a person cannot be awakened. People in a coma are unconscious. A coma can be caused by many things. Two causes are untreated low blood sugar (hypoglycemia) and a metabolic crisis., sometimes leading to death
A metabolic crisis can be triggered by:
- eating large amounts of protein
- illness or infection
- going too long without food
- stressful events such as surgery
Between episodes of metabolic crisis, children with PA are often healthy.
Long-term effects are seen in some children and adults with PA. These can include:
- learning problems or intellectual disabilities
- delays in walking and motor skills
- abnormal involuntary movements (dystonia or This describes episodes of involuntary jerking movements combined with movements that are often irregular and twisting. These movements can flow from one body part to another. They commonly affect the arms, legs, trunk, and the muscles of the face.)
- rigid muscle tone, called This is rigidity of the muscles and increased reflexes. It is caused by increased muscle tone. It results in abnormal tightness or stiffness of the muscles and joints.
- poor growth with short stature
- This is a condition that causes the bones to become thinner over time. People with this condition have a higher chance for bone fractures.
- inflammation of the This is a large organ behind the stomach. One of its jobs is to make digestive enzymes and release them into the small intestine. The digestive enzymes are essential for food (carbohydrates, proteins and fats) to be broken down into small enough nutrients to get into the blood. Without them, people cannot absorb enough nutrients and will develop malnutrition and poor growth. The pancreas also makes the hormone insulin which is needed for glucose (sugar) to leave the blood and get into body cells., called This happens when the pancreas, an organ near the stomach, becomes inflamed. It causes severe abdominal pain. It can be caused by some metabolic disorders, gallstones or too much alcohol.
- vision loss due to problems with the nerves in the eye
- This is a condition in which the ovaries stop working too early (earlier than age 40). This causes the menstrual periods to stop. It is found only in about 1% of all women. It is sometimes caused by diabetes, other hormone disorders, autoimmune disorders, and can be a result of cancer treatments or other medications. It often occurs in women with galactosemia. Symptoms include hot flashes, mood swings, night sweats, vaginal dryness and infertility.
- kidney problems
- liver problems
- heart problems
Without treatment, brain damage can occur. This can result in intellectual disabilities. If not treated, many babies with PA die within the first year of life.
A small number of people with PA never show symptoms and are only found to be affected after a brother or sister is diagnosed.
WHAT IS THE TREATMENT FOR PA?
Your baby’s primary doctor will work with a This is a doctor or medical geneticist who has special training in diagnosing and treating metabolic disorders. They often work in university hospitals or large medical centers. and a dietician to provide care for your child.
Prompt treatment is needed to prevent intellectual disabilities and serious medical problems. Most children need to be on a low-protein diet and drink a special medical formula. You should start the diet and formula as soon as you know your child has PA.
The following are treatments often recommended for children with PA:
1. Low-protein diet, medical foods and medical formula
A food plan with low amounts of the amino acids This is one of 20 amino acids that make up protein. It is not made by the body and must be eaten in the diet. It is found in all foods that contain protein., valine, methionine, and threonine, and with limited amounts of protein is often recommended. Most food in the diet will be carbohydrates (bread, cereal, pasta, fruit, vegetables, etc.). This is one of the three types of nutrients in food (carbohydrates, fats, proteins). Sugars and starches are the most important types of carbohydrates. They are broken down by the body into glucose, the main source of energy for the body. Carbohydrates are found in foods such as: bread, cereal, pasta, grains, fruits and vegetables. Milk and dairy products, fruit drinks, sugar, candy, and sweet desserts also contain carbohydrates. give the body many types of sugar that can be used as energy. Eating a diet high in carbohydrates and low in protein can help prevent metabolic crises.
Foods high in protein that may need to be avoided or limited include:
- milk and dairy products
- meat and poultry
- dried beans and legumes
- nuts and peanut butter
Many vegetables and fruits have only small amounts of protein and can be eaten in carefully measured amounts. Do not remove all protein from the diet. Children with PA need a certain amount of protein to grow properly.
Your This is a person with special training in food and nutrition. A registered dietician (RD) has met the necessary educational requirements and has passed a national examination. If your child has a metabolic disorder, it is important for you to work with a registered dietician. They help create healthy food plans for people with metabolic disorders or other special needs. will create a food plan that contains the right amount of protein, nutrients, and energy to keep your child healthy. Your child will need to be on a special food plan throughout his or her life.
Medical formula and foods
In addition to a low-protein diet, your child may be given a special medical formula. This formula contains the correct amount of protein and nutrients needed for normal growth and development. Your metabolic doctor and dietician will tell you what type of formula is best and how much to use.
There are also medical foods such as special low protein flours, pastas, and rice that are made especially for people with organic acid disorders. Your dietician will tell you how to use these foods as part of your child’s diet.
Some states offer help with payment, or require private insurance to pay for the formula and other special medical foods.
2. Avoid going a long time without food
Infants and young children with PA need to eat frequently to prevent a metabolic crisis. Your metabolic doctor will tell you how often your child needs to be fed. In general, it is often suggested that infants be fed every four to six hours. Some babies need to eat even more frequently than this. It is important that infants be fed during the night. They may need to be woken up to eat if they do not wake up on their own. Your metabolic doctor and dietician will give you an appropriate feeding plan for your infant. Your doctor will also give you a ‘sick day’ plan, tailored to your child’s needs, for you to follow during illnesses or other times when your child will not eat.
Your metabolic doctor will continue to advise you on how often your child should eat as he or she gets older.
Children with PA may benefit by taking This is a natural substance found in muscle cells. It helps the body make energy from the fat in food and the fat stored in the body. It also helps the cells get rid of harmful wastes made during the breakdown of fat. Carnitine supplements may be used as a treatment for some metabolic disorders.. This is a safe and natural substance that helps the body make energy. It also helps get rid of harmful wastes. L-carnitine is part of the usual treatment for PA. Your doctor will tell you how much your child needs. Unless you are advised otherwise, use only L-carnitine prescribed by your doctor.
Certain antibiotics, taken by mouth, can help reduce the amount of propionic acid in the intestines. Your doctor will decide if your child needs antibiotics and, if so, what type.
Some children may be given biotin supplements by mouth. This is one type of B vitamin. It helps break down fat, protein, and carbohydrates from food for use by the body. Biotin is found in chicken, salmon, cheese, eggs, and some vegetables. It can also be bought in pill form. Children with certain metabolic disorders may be treated with biotin supplements. is a type of B vitamin that helps the body make energy from food. Biotin has not been proven to help in PA, but your doctor may talk with you about trying this supplement to see if it is of benefit to your child.
Children who are having symptoms of a metabolic crisis should be treated in the hospital. During a metabolic crisis, your child may be given medications such as This is a substance that lowers the amount of acid in the blood. It is sometimes used as part of the treatment for children with certain organic acid disorders. by This is a small tube placed into a vein, usually in the hand or arm. Medications and nutrients can be given through this tube directly into the blood. IV’s are often used in the hospital to give fluids, glucose and medication over a long period of time. to help reduce the acid levels in the blood. This is a type of sugar made from the carbohydrates in food. Glucose is found in the blood. It is the main source of energy for the body and brain. is often given by IV to prevent the breakdown of protein and Fat is one of the three main nutrients in food (carbohydrates, fat, protein). Some foods that contain fat are butter, margarine, oils, nuts, meats, poultry, fish and some dairy products. Extra calories from food are stored as body fat. Stored body fat provides the body with a reserve supply of energy. stored in the body. Carglumic acid (Carbaglu®) may be given to manage high blood This is a waste product made when protein is broken down for the body to use. Ammonia is harmful to the body. It is usually changed to a harmless substance called “urea.” Urea is then removed from the body in the urine. People with urea cycle disorders cannot get rid of ammonia. If these conditions are not treated, ammonia can build up and cause serious health problems. levels.
Do not use any medication or supplement without first checking with your doctor or metabolic doctor.
4. Regular blood and urine tests
The process of testing a disease for a person who does not appear to have the disease (non-symptomatic or asymptomatic). The goal of tracking is to find the disease in its earliest stages. of These are substances made when the body breaks down fat (fatty acids) for energy. In people with certain metabolic disorders or diabetes, ketones can build up in the blood and spill over into the urine. If ketones build up in the blood, they can cause acidosis which can lead to serious health problems.
Your child will have periodic urine tests to check the level of ketones. These can be done at home or at the doctor’s office. Ketones are substances formed when body fat is broken down for energy. This can happen after going without food for long periods of time, as the result of an illness, or during periods of heavy exercise. Ketones in the urine may signal the start of a metabolic crisis.
Your child will have regular blood tests to measure the levels of amino acids. Urine tests may also be done. Your child’s diet and medication may need to be adjusted based on the results of these tests.
5. Call your doctor at the start of any illness
In children with PA, even minor illnesses can lead to a metabolic crisis. In order to prevent problems, call your doctor right away when your child has any of the following:
- loss of appetite
- infection or illness
Children with PA need to eat more starchy foods and drink more fluids when they are ill – even if they aren’t hungry – or they could have a metabolic crisis. In addition, they should avoid eating protein during any illness.
Many children with PA need to be treated in the hospital during an illness to avoid serious health problems. Ask your metabolic doctor if you should carry a special travel letter with medical instructions for your child’s care.
6. Liver transplant
Liver transplant surgery is an optional treatment for people with PA. The PCC enzyme that causes PA is located in the liver. Because of this, some children with PA have had liver transplantation surgery (removal of their liver and replacement with a donor liver) to treat their PA symptoms.
A liver transplant is a major surgical procedure and is associated with risks. Individuals who have a liver transplant must take medication for the rest of their lives to prevent their body from rejecting the donor liver. Even with a successful liver transplantation, people with PA may still need to have a restricted diet. A liver transplant helps with some but not all of the symptoms of PA.
Many factors must be considered before surgery and this option should be discussed thoroughly with your child’s physicians.
WHAT HAPPENS WHEN PA IS TREATED?
Babies who have prompt and ongoing treatment before they have a metabolic crisis may have normal growth and development. In general, the earlier treatment is started, the better the outcome.
Even with treatment, some children have life-long learning problems or intellectual disabilities. Seizures or problems with involuntary movements also occur in some children, despite treatment. Children with PA often have more infections than usual. These need to be treated promptly to avoid a metabolic crisis.
WHAT CAUSES THE PCC ENZYME TO BE ABSENT OR NOT WORKING CORRECTLY?
Genes tell the body how to make enzymes. The PCCA and the PCCB A segment of DNA that contains the instructions to make a specific protein (or part of a protein). Genes are contained on chromosomes. Chromosomes, and the genes on those chromosomes, are passed on from parent to child. Errors in the DNA that make up a gene are called variants and can lead to diseases. instruct the body to make the PCCA enzyme. Everyone has two copies of the PCCA and the PCCB genes. People with PA have changes, also called A variant is a change or alteration in a person’s DNA sequence. Variants can happen in genes and affect how the gene functions. There are different types of variants – they can be non-problem causing (benign), disease-causing (pathogenic) or of unknown significance. The term variants is now used in place of the term mutation. in both copies of either their PCCA genes or their PCCB genes that cause these genes to not work correctly. Because of the variants in either the PCCA or the PCCB genes, the PCC enzyme either does not work properly or is not made at all.
HOW IS PA INHERITED?
PA is inherited in an autosomal recessive manner. It affects both boys and girls equally. Everyone has two copies of the PCCA and the PCCB genes that make the PCC enzyme. In children with PA, one of these sets of genes (either PCCA or PCCB) does not work correctly. These children inherit one non-working gene for PA from each parent.
Parents of children with PA rarely have the disorder themselves. Instead, each parent has a single non-working gene for PA. They are called A person who has one copy of a gene mutation for a particular autosomal recessive disorder (remember genes come in pairs). Carriers are not affected by the disorder. However, they can pass on the gene variant to their children. Children who inherit two such gene variants will be affected by the disorder. The term variants is now used in place of the term mutation.. Carriers do not have PA because their other gene is working correctly.
When both parents are carriers, there is a 25% chance in each pregnancy for the child to have PA. There is a 50% chance for the child to be a carrier, just like the parents. And, there is a 25% chance for the child to have two working genes.
Relating to (or due to) genes and heredity or the field of studying genes and heredity. counseling is available to families who have children with PA. Genetic counselors can answer your questions about how PA is inherited, choices during future pregnancies, and how to test other family members. Ask your doctor about a referral to a These are health care providers who have special training in genetic conditions. They help families understand genetic disorders and how they are passed down. Genetic counselors offer information and support to people who have genetic conditions in their families or are concerned that they may have a child with an inherited disorder..
IS GENETIC TESTING AVAILABLE?
Genetic testing for PA can be done on a blood sample. Genetic testing, also called DNA testing, looks for changes called variants in the genes that causes PA. Talk with your genetic counselor or metabolic doctor if you have questions about Deoxyribonucleic acid (DNA) is a molecule found in the chromosomes that carries genetic information. DNA is composed of four units (called bases) that are designated A, T, G, and C. The sequence of the bases spell out instructions for making all of the proteins needed by an organism. A gene is a section of DNA that holds the instructions for a specific protein. A change in one or more of the DNA bases making up a gene is called a mutation. Some mutations change the protein instructions and can lead to particular health problems or disorders. Each parent passes half of their chromosomes, and thus half of their DNA instructions, onto their children. It is these instructions that cause certain traits, such as eye or hair color, to be inherited. testing.
DNA testing is not necessary to diagnose your child. However, it can be helpful for carrier testing or prenatal diagnosis, discussed below.
WHAT OTHER TESTING IS AVAILABLE?
Special tests on blood, urine, or skin samples can be done to confirm PA. Talk to your metabolic doctor or genetic counselor if you have questions about testing for PA.
CAN YOU TEST DURING A FUTURE PREGNANCY?
If both gene changes (variants) have been found in your child with PA, DNA testing can be done during future pregnancies. The sample needed for this test is obtained by either CVS or This is a test done during pregnancy. A needle is used to remove a small sample of fluid from the sac around the fetus. The sample can be used to test for certain genetic disorders in the fetus. Amniocentesis to test for genetic conditions is usually done between 13 and 20 weeks of pregnancy..
PA can also be found through an enzyme test using cells from the fetus. The sample needed for this test is obtained by amniocentesis.
Parents may either choose to have testing during pregnancy or wait until birth to have the baby tested. Parents may also choose to use assisted reproductive techniques to decrease the chance that their future children would have PA. A genetic counselor can talk to you about your choices and answer questions about prenatal testing or testing your baby after birth.
CAN OTHER MEMBERS OF THE FAMILY HAVE PA OR BE CARRIERS?
Older brothers and sisters of a baby with PA, if they are healthy and growing normally, are unlikely to have the condition. However, finding out if other children in the family have this condition may be important because treatment can prevent serious health problems. Ask your metabolic doctor or genetic counselor whether your other children should be tested.
Brothers and sister who do not have PA still have a chance to be carriers like their parents. Except in special cases, carrier testing should only be done on people over 18 years of age.
If you are a parent of a child with PA, your brothers and sisters have a 50% chance to be a PA carrier. It is important for other family members to be told that they could be carriers. There is a small chance they are also at risk to have children with PA.
All states offer newborn screening for PA. However, when both parents are PA carriers, A screening test that looks for different disorders using a small sample of blood taken from a newborn’s heel. A positive or abnormal newborn screening result means that there are slight differences that were found in the baby’s blood, and further testing is needed to figure out if the baby has a metabolic disorder. results are not sufficient to rule out the condition in a newborn baby. In this case, special diagnostic testing should be done in addition to newborn The process of testing for disease in a person who does not show signs of having the disease (nonsymptomatic or asymptomatic person). The goal of screening is to catch the disease in its early stages..
CAN OTHER FAMILY MEMBERS BE TESTED?
Brothers and sisters of a child with PA can have special tests done on blood, urine, or skin samples. Talk to your doctor or genetic counselor if you have questions about testing for PA.
Carrier testing for PA may be available. If you have questions about carrier testing, ask your genetic counselor or metabolic doctor.
HOW MANY PEOPLE HAVE PA?
About 1 in every 100,000 babies in the United States is born with PA.
DOES PA HAPPEN MORE OFTEN IN A CERTAIN ETHNIC GROUP?
PA occurs in all ethnic groups around the world. It is found more often in the Arab population of Saudi Arabia and the Inuit population of Greenland. About one in 2000 to 5000 babies of Saudi Arabian ancestry is born with PA. And, about one in 1000 babies in the Inuit population of Greenland has PA.
DOES PA GO BY ANY OTHER NAMES?
PA is sometimes also called:
- Propionyl-CoA carboxylase deficiency
- PCC deficiency
- Ketotic glycinemia
- Ketotic hyperglycinemia
WHERE CAN I FIND MORE INFORMATION?
Propionic Acidemia Foundation
Propionic Acidemia Research Network
Organic Acidemia Association
Metabolic Support UK
Baby’s First Test
|Reviewed by:||HI, CA, OR, and WA metabolic specialists|
|Review date:||September 31, 2007
May 1, 2011
August 23, 2013
July 11, 2016
May 9, 2020
March 5, 2023
|Update on:||March 5, 2023|
THIS INFORMATION DOES NOT PROVIDE MEDICAL ADVICE. All content (“Content”), including text, graphics, images and information are for general informational purposes only. You are encouraged to confer with your doctor or other health care professional with regard to information contained on this information sheet. After reading this information sheet, you are encouraged to review the information carefully with your doctor or other healthcare provider. The Content is not intended to be a substitute for professional medical advice, diagnosis or treatment. NEVER DISREGARD PROFESSIONAL MEDICAL ADVICE, OR DELAY IN SEEKING IT, BECAUSE OF SOMETHING YOU HAVE READ ON THIS INFORMATION SHEET. This project is supported by a grant from the Having to do with the mother. and Child Health Bureau, Health Resources and Service Administration, Genetic Services Branch, MCH Project #:UH7MC30774-01-00 http://mchb.hrsa.gov