ORGANIC ACID DISORDER
Disease name: Glutaric acidemia, type 1
- What is GA-1?
- What causes GA-1?
- If GA-1 is not treated, what problems occur?
- What is the treatment for GA-1?
- What happens when GA-1 is treated?
- What causes the glutaryl-CoA dehydrogenase enzyme to be absent or not working correctly?
- How is GA-1 inherited?
- Is genetic testing available?
- What other testing is available?
- Can you test during a future pregnancy?
- Can other members of the family have GA-1 or be carriers?
- Can other family members be tested?
- How many people have GA-1?
- Does GA-1 happen more often in a certain ethnic group?
- Does GA-1 go by any other names?
- Where can I find more information?
This fact sheet contains general information about GA-1. 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 GA-1 should be followed by a metabolic doctor in addition to their primary doctor.
WHAT IS GA-1?
GA-1 stands for “glutaric acidemia, type 1.” It is one type of organic acid disorder. People with GA-1 have problems breaking down the amino acids lysine, This is an amino acid made by the body. When it is broken down, it makes glutaric acid., and tryptophan 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 GA-1?
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.
GA-1 is caused by problems with the enzyme called “glutaryl-CoA dehydrogenase” (GCDH). In people with GA-1, the GCDH enzyme is either missing or not working properly. This enzyme’s job is to break down a substance called glutaryl-CoA. Glutaryl-CoA is made when the amino acids lysine, hydroxylysine, 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. are processed. When glutaryl-CoA cannot be removed, it causes glutaric acid and other harmful substances to build up in the blood and cause problems. Lysine and tryptophan are found in all foods that contain protein.
IF GA-1 IS NOT TREATED, WHAT PROBLEMS OCCUR?
Babies with GA-1 are usually healthy at birth, although many are born with a larger than average head size. Other symptoms usually start between two months and four years of age.
GA-1 causes episodes of severe illness called metabolic crises. Some of the first symptoms of a 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. are:
- poor appetite
- extreme sleepiness or lack of energy
- low muscle tone (floppy muscles and joints)
- muscle weakness
If untreated, other symptoms then follow:
- tics or spasms of the muscles
- rigid muscle contractions, 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.
- involuntary jerking movements of the arms and legs, called This is a condition that causes muscle spasms. These spasms can force the body into awkward and sometimes painful positions. It commonly affects the arms and the legs but can occur in any part of the body. People with dystonia also have episodes of involuntary jerking movements.
- poor coordination and balance problems
- increased 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.
- 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 or blood in the brain
- 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
Episodes of metabolic crisis are often triggered by:
- illness or infection
- going without food for long periods of time
Other effects of GA-1 that can happen even without a metabolic crisis are:
- poor growth
- enlarged liver
- 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.
- progressive spasticity
- dystonia, an involuntary movement disorder
- repeated episodes of fever
- excessive sweating
- delays in walking and other motor skills
- learning delays and intellectual disabilities
- speech problems
- brain damage
- kidney disease
Some people have very mild or no symptoms and are only found to be affected after a brother or sister is diagnosed.
WHAT IS THE TREATMENT FOR GA-1?
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 care for your child.
Prompt treatment is needed to prevent episodes of metabolic crisis. You need to start treatment as soon as you know your child has GA-1. Certain treatments may be advised for some children but not others. Treatment is usually needed throughout life.
The following are treatments often recommended for babies and children with GA-1:
This is a one type of B vitamin (vitamin B2). It helps change carbohydrates, protein, and fat into energy for the body. Some foods high in riboflavin are dairy products, yogurt, cheese, meats, poultry, whole and enriched grains, and green vegetables. Some children with metabolic disorders may be helped by taking riboflavin supplements. is a vitamin that helps the body process protein. It may also help lessen the amount of This is a harmful waste product made when certain amino acids (lysine, tryptophan and hydroxylysine) are broken down in the body. made by the body. Your doctor may recommend that your child take riboflavin supplements by mouth.
Some children may be helped by 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 body cells make energy. It also helps the body get rid of harmful wastes. Your doctor will decide whether or not your child needs L-carnitine supplements. Unless you are advised otherwise, use only L-carnitine prescribed by your doctor.
Do not use any medication without checking with your metabolic doctor.
Children with symptoms of a metabolic crisis need medical treatment right away. They often need to be treated in the hospital. During a metabolic crisis, children may be given fluids, 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., This is a hormone made in the pancreas. It controls the level of glucose (sugar) in the blood., carnitine, and other medications by IV to help get rid of harmful substances in the blood. Ask your metabolic doctor if you should carry a special travel letter with medical instructions for your child’s care.
2. Avoid going a long time without food
Infants and young children with GA-1 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 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 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. When they are well, many older children and adults with GA-1 can go without food for up to 12 hours without problems. They may need to continue the other treatments throughout life.
3. Food plan, including medical foods and formula
Most children need to eat a diet made up of foods low in lysine and tryptophan. Special medical foods and a special formula are usually part of the diet. Your dietician will create a food plan that has the right amount of protein, nutrients, and energy for your child.
Low-protein (lysine and tryptophan) diet
Foods that will need to be avoided or strictly limited include:
- milk, cheese, and other dairy products
- meat and poultry
- dried beans and legumes
- nuts and peanut butter
Many vegetables and fruits have only small amounts of lysine and tryptophan and can be eaten in carefully measured amounts.
Do not remove all protein from the diet. Your child still needs a certain amount of protein for normal growth and development. Any changes in the diet should be made under the guidance of a dietician familiar with GA-1.
Medical foods and formula
There are medical foods such as special low-protein flours, pastas, and rice that are made especially for people with organic acid disorders.
A special medical formula that contains the right level of amino acids and nutrients for your child may be recommended. Your metabolic doctor and dietician will tell you whether your child should be on this formula and how much to use. Some states offer help with payment for this formula, and others require private insurance to pay for the formula and other special medical foods.
Your child’s exact food plan will depend on many things such as his or her age, weight, general health, and blood test results. Your dietician will fine-tune your child’s diet over time.
The long-term benefits of the special diet and medical foods are not yet known. However, it is important to follow the food plan as long as your doctor advises.
4. Regular blood tests
Your child will have regular blood tests to measure his or her amino acid levels. Urine tests may also be done. Your child’s diet and medication may need to be adjusted based on blood and urine test results.
5. Call your doctor at the start of any illness
For some babies and children, 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
- low energy or extreme sleepiness
- infection or illness
- behavior or personality changes
Children with GA-1 need to eat more carbohydrates and drink more fluids when they are ill – even if they’re not hungry – or they could have a metabolic crisis.
Children who are sick often don’t want to eat. If they can’t eat, or if they show signs of a metabolic crisis, they may need to be treated in the hospital. Ask your metabolic doctor if you should carry a special travel letter with medical instructions for your child’s care.
WHAT HAPPENS WHEN GA-1 IS TREATED?
With prompt and lifelong treatment, children with GA-1 can often live healthy lives with typical growth and learning. Early treatment can help prevent episodes of metabolic crisis and the resulting health effects.
Even with treatment, some children continue to have episodes of metabolic crisis. This can lead to brain damage and long-term problems with involuntary movements and spasticity. After age six, metabolic crises are less common.
WHAT CAUSES THE GLUTARYL-COA DEHYDROGENASE ENZYME TO BE ABSENT OR NOT WORKING CORRECTLY?
Genes tell the body how to make enzymes. The GCDH gene instructs the body to make the glutaryl-CoA dehydrogenase enzyme. Everyone has two copies of the GCDH gene. People with GA-1 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 their GCDH 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.. Because of the variants in the GCDH genes, the glutaryl-CoA dehydrogenase enzyme either does not work properly or is not made at all.
HOW IS GA-1 INHERITED?
GA-1 is inherited in an autosomal recessive manner. It affects both boys and girls equally.
Everyone has two copies of the GCDH gene that make the glutaryl-CoA dehydrogenase enzyme. In children with GA-1, neither of their GCDH genes works correctly. These children inherit one non-working GCDH gene for the condition from each parent.
Parents of children with GA-1 rarely have the condition themselves. Instead, each parent has a single non-working gene for GA-1. 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 GA-1 because their other GCDH gene is working correctly.
When both parents are carriers, there is a 25% chance in each pregnancy for the child to have GA-1. 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 GA-1. Genetic counselors can answer your questions about how the condition 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 GA-1 can be done on a blood sample. Genetic testing, also called DNA testing, looks for changes (variants) in the pair of genes that cause GA-1.
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 is not necessary to diagnose your child. It can be helpful for carrier or prenatal testing, discussed below.
WHAT OTHER TESTING IS AVAILABLE?
Special tests on blood, urine, or skin samples can be done to confirm GA-1. Talk to your metabolic doctor or genetic counselor if you have questions about testing for GA-1.
CAN YOU TEST DURING A FUTURE PREGNANCY?
If both gene changes (variants) have been found in your child, 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..
Parents may 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 GA-1. 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 GA-1 OR BE CARRIERS?
The brothers and sisters of a baby with GA-1 have a chance of being affected, even if they haven’t had symptoms. Finding out whether other children in the family have GA-1 is important because early treatment may prevent serious health problems. Talk to your metabolic doctor or genetic counselor about testing your other children.
Brothers and sisters who do not have GA-1 still have a chance to be carriers like their parents. Except in special cases, carrier testing should only be done in people over 18 years of age.
If you are a parent of a child with GA-1, your brothers and sisters have a 50% chance to be a 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 GA-1.
All states offer newborn screening for GA-1. However, when both parents are 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 GA-1 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 GA-1 can be tested using blood, urine, or skin samples.
If both gene changes have been found in your child, other family members can have DNA testing to see if they are carriers.
If DNA testing would not be helpful, other methods of carrier testing may be available. Your metabolic doctor or genetic counselor can answer your questions about carrier testing.
HOW MANY PEOPLE HAVE GA-1?
About one in every 40,000 white babies in the United States is born with GA-1.
DOES GA-1 HAPPEN MORE OFTEN IN A CERTAIN ETHNIC GROUP?
GA-1 occurs in people from all parts of the world. It is more common in people of Amish background in the United States, the Ojibway Indian population in Canada, and people of Swedish ancestry.
DOES GA-1 GO BY ANY OTHER NAMES?
GA-1 is sometimes also called:
- Glutaric aciduria type 1
- Glutaryl-CoA dehydrogenase deficiency
- Dicarboxylic aminoaciduria
- Glutarate-aspartate transport defect
WHERE CAN I FIND MORE INFORMATION?
Organic Acidemia Association
Metabolic Support UK
Genetics Home Reference
Save Babies through Screening Foundation
Baby’s First Test
|Reviewed by:||HI, CA, OR, and WA metabolic specialists|
|Review date:||May 20, 2020
August 26, 2013
June 6, 2011
September 31, 2007
|Update on:||May 20, 2020|
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