VLCADD (very long chain acyl-CoA dehydrogenase deficiency)
FATTY ACID DISORDER
Disorder Name: Very long chain acyl-CoA dehydrogenase
- What is VLCADD?
- What causes VLCADD?
- If VLCADD is not treated, what problems occur?
- What is the treatment for VLCADD?
- What happens when VLCADD is treated?
- What causes the VLCAD enzyme to be absent or not working correctly?
- How is VLCADD inherited?
- Is genetic testing available?
- What other testing is available?
- Can you test during a future pregnancy?
- Can other members of the family have VLCADD or be carriers?
- Can other family members be tested?
- How many people have VLCADD?
- Does VLCADD happen more often in a certain ethnic group?
- Does VLCADD go by any other names?
- Where can I find more information?
This fact sheet contains general information about VLCADD. Every child is different and some of this information may not apply to your child specifically. Certain treatments may be recommended for some children but not others. Children with VLCADD should be followed by a metabolic doctor in addition to their primary doctor.
WHAT IS VLCADD?
VLCADD stands for “very long chain acyl-CoA dehydrogenase deficiency.” It is one type of fatty acid oxidationThis is the process used by the body to change fatty acids, the building blocks of fat, into energy. It happens in the mitochondria – the small energy-producing parts found in each cell of the body. disorder. People with VLCADD have problems breaking down certain types of fat into energy for the body.
|Fatty Acid Oxidation Disorders:
Fatty acid oxidation disorders (FAODs)This is a group of rare inherited conditions. FAODs are caused by missing or non-working enzymes. Normally, many enzymes are used by the body to break down fat into energy. In people with FAODs, one of these enzymes is not working and fat cannot be used for energy. If these conditions are not treated, they can lead to serious health problems. are a group of rare inheritedAcquiring 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 enzymesA 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 break down fats in the body (a process called fatty acid oxidation). Problems with any of these enzymes can cause a fatty acid oxidation disorder. People with FAODs cannot properly break down fatFat 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. from either the food they eat or from fat stored in their bodies.
The symptoms and treatment vary between different FAODs. They can also vary from person to person with the same FAOD. See the fact sheets for each specific FAOD.
FAODs are inherited in an autosomal recessive manner and affect both males and females.
WHAT CAUSES VLCADD?
VLCADD is caused by problems with the enzyme “very long chain acyl-CoA dehydrogenase” (VLCAD). In people with VLCADD, the VLCAD enzyme is either missing or not working properly. This enzyme’s job is to break down certain fats from the food we eat into energy. It also breaks down fat already stored in the body.
Energy from fat keeps us going whenever our bodies run low of their main source of energy, a type of sugar called glucoseThis 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.. Our bodies rely on fat when we don’t eat for a stretch of time – like when we miss a meal or when we sleep.
When the VLCADD enzyme is missing or not working, the body cannot break down fat for energy and must rely solely on glucose. Although glucose is a good source of energy, there is a limited amount available. Once the glucose has been used up, the body tries to use fat without success. This leads to low blood sugar, called hypoglycemiaThis happens when there is too little sugar (glucose) in the blood. It may cause a person to feel nervous, shaky, weak, or sweaty. It may also cause headache, blurred vision, and hunger. If left untreated, it can cause unconsciousness (coma) and sometimes even death., and to the build up of harmful substances in the blood.
IF VLCADD IS NOT TREATED, WHAT PROBLEMS OCCUR?
VLCADD is variable and can cause mild effects in some people and more serious health problems in others. Symptoms may start in infancy or not until adulthood. There are three types of VLCADD: Early, Childhood, and Adult.
It is common for babies and children with the early and childhood types of VLCADD to have episodes of illness called metabolic crises. Some of the first symptoms of a metabolic crisisThis 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:
- extreme sleepiness
- behavior changes
- irritable mood
- poor appetite
Some of these other symptoms may also follow:
If a metabolic crisis is not treated, a child with VLCADD can develop:
- breathing problems
- seizuresThese 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.
- comaThis 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
Periods of hypoglycemia can happen with or without the other symptoms. Hypoglycemia can cause a child to feel weak, shaky, or dizzy with clammy, cold skin. If not treated, it can lead to a coma, and possibly death.
Either hypoglycemia or a full metabolic crisis can occur:
- after going too long without food
- during illness or infection
- after heavy exercise
Symptoms of early and childhood VLCADD often happen after a period of having nothing to eat for more than a few hours. Symptoms are also more likely when a child with VLCADD gets sick or has an infection.
About half of babies diagnosed with VLCADD have the early type. They usually start to show effects between birth and 4 months. In addition to metabolic crises, babies can also have:
- enlarged heart, irregular heartbeat, and other heart problems
- enlarged liver and other liver problems
- muscle problems
If not treated, babies with early VLCADD usually die young.
About one third of people with VLCADD have the childhood type. They usually show symptoms in late infancy or early childhood. Episodes of hypoglycemia or full metabolic crisis happen during illness or after long periods of not eating. Other effects can include:
- enlarged liver
- other liver problems
- muscle weakness, especially after exercise
Heart problems are usually not seen in childhood VLCADD.
Some children with VLCADD have never had symptoms and are only found to be affected after a brother or sister has been diagnosed.
About one fifth of people with VLCADD have the adult type. They usually show symptoms starting in the teen years or in adulthood. Periods of muscle weakness are common. Breakdown of muscle fibers can occur. This usually happens during heavy exercise or after going without food for a long period of time.
Signs of muscle breakdown are:
- muscle aches
- reddish-brown color to the urine
Adults with muscle symptoms who do not get treatment can develop kidney failure.
People with the adult type of VLCADD usually do not have heart problems, hypoglycemia, or metabolic crises.
WHAT IS THE TREATMENT FOR VLCADD?
Your baby’s primary doctor will work with a metabolic doctor to care for your child. Your doctor may also suggest that you meet with a dietician familiar with VLCADD.
Certain treatments may be advised for some children but not others. When necessary, treatment is usually needed throughout life. The following are treatments often recommended for children with VLCADD:
1. Avoid going a long time without food
Infants and young children with VLCADD need to eat frequently to prevent a metabolic crisis. Your metabolic doctorThis 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. 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 dieticianThis 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 teens and adults with VLCADD can go without food for up to 12 hours without problems. The other treatments usually need to be continued throughout life.
Sometimes a low fat, high carbohydrate food plan is recommended. CarbohydratesThis 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 may types of sugar that can be used as energy. In fact, for children needing this treatment, most food in the diet should be carbohydrates (bread, pasta, fruit, etc.) and protein (lean meat and low-fat dairy foods). Any diet changes should be made under the guidance of an experienced dietician.
People with VLCADD cannot use certain building blocks of fat called long-chain fatty acidsThis is one of many types of fatty acids, the building blocks of fat. Long-chain fatty acids are made up of chains of 12 or more carbon atoms.. Your dietician can help create a food plan low in these fats. Much of the rest of fat in the diet may be in the form of medium-chain fatty acidsThis is one of many types of fatty acids, the building blocks of fat. Medium-chain fatty acids are made up of chains of 4 to 12 carbon atoms..
Ask your doctor whether your child needs to have any changes in his or her diet.
3. Medium chain triglycerides
Medium Chain Triglyceride (MCT) are often used as part of the food plan for people with VLCADD. MCTs are available in MCT oil and in triheptanoin (DOJOLVI ®) – a medication made of MCTs. These supplements have medium chain fatty acidsThese are the building blocks of fat. Fat from food is broken down by enzymes into fatty acids. These are changed by other enzymes and are used as energy or stored as body fat. Some types of fatty acids are: short-chain, medium-chain, long-chain, and very-long chain. that can be used in small amounts for energy. Your metabolic doctor or dietician can tell you how to use these supplements. You will need to get a prescription from your doctor to get these MCTs supplements.
4. L-CarnitineThis 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. and other supplements
Some children may be helped by taking L-carnitine. This is a safe and natural substance that helps the body make energy. It also helps the body get rid of harmful wastes. Your doctor will decide whether your child needs L-carnitine. Unless you are advised otherwise, use only L-carnitine prescribed by your doctor.
Other supplements may be advised in infants with severe disease.
Do not use any medications or supplements without checking with your doctor.
5. Call your doctor at the start of any illness
Always call your health care provider when your child has any of the following:
- poor appetite
- low energy or excessive sleepiness
- an infection
- a fever
- persistent muscle pain, weakness, or reddish-brown color to the urine
Children with VLCADD need to eat extra starchy food and drink more fluids during any illness – even if they may not feel hungry – or they could develop hypoglycemia or a metabolic crisis. When they become sick, children with VLCADD often need to be treated in the hospital to prevent serious health problems.
Ask your metabolic doctor if you should carry a special travel letter with medical instructions for your child’s care.
6. Avoid prolonged exercise or exertion
Long periods of exercise can also trigger symptoms. Problems occurring during or after exercise can include:
- muscle aches
- reddish-brown color to the urine
If muscle symptoms happen, prompt treatment is needed to prevent kidney damage. Children and adults with muscle symptoms should:
- drink fluids right away
- eat something starchy or sugary
- get to a hospital for treatment
To help prevent muscle symptoms:
- avoid prolonged or heavy exercise
- keep the body warm
- eat carbohydrates before and during periods of moderate exercise
WHAT HAPPENS WHEN VLCADD IS TREATED?
With prompt and careful treatment, people with the childhood and adult types of VLCADD can often live healthy lives with typical growth and development.
Before diagnosis through newborn screening was available, the early type of VLCADD was fatal. Now, with immediate and ongoing treatment, many infants with VLCADD are surviving.
WHAT CAUSES THE VLCAD ENZYME TO BE ABSENT OR NOT WORKING CORRECTLY?
Genes tell the body how to make enzymes. The ACADVL gene instructs the body to make the VLCAD enzyme. Everyone has two copies of the ACADVL gene. People with VLCADD have changes, also called variantsA 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 ACADVL genesA 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. that cause them to not work correctly. Because of the variants in the ACADVL genes, the VLCAD enzyme either does not work properly or is not made at all.
HOW IS VLCADD INHERITED?
VLCADD is inherited in an autosomal recessive manner. It affects both boys and girls equally.
Everyone has two copies of the ACADVL gene that make the VLCAD enzyme. In children with VLCADD, neither of their ACADVL genes works correctly. These children inherit one non-working ACADVL gene from each parent.
Parents of children with VLCADD are rarely affected with the disorder. Instead, each parent has a single non-working ACADVL gene. They are called carriersA 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 VLCADD because their other ACADVL gene is working correctly.
When both parents are carriers, there is a 25% chance in each pregnancy for the child to have VLCADD. 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.
GeneticRelating to (or due to) genes and heredity or the field of studying genes and heredity. counseling is available to families who have children with VLCADD. Genetic counselors can answer your questions about how VLCADD is inherited, options during future pregnancies, and how to test other family members. Ask your doctor about a referral to a genetic counselorThese 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 VLCADD can be done on a blood sample. Genetic testing, also called DNA testing, looks for changes (variants) in the pair of genes that causes VLCADD.
DNADeoxyribonucleic 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 often used to diagnose VLCADD in children. In addition to establishing a diagnosis, DNA testing can also tell what type of VLCADD a person has – early, childhood, or adult. It can also be helpful for carrier testing or prenatal diagnosis, discussed below. Talk with your metabolic doctor or genetic counselor about whether DNA testing for VLCADD would be helpful to you.
WHAT OTHER TESTING IS AVAILABLE?
VLCADD can be confirmed by a special test called a “fatty acid oxidation probe” using a skin sample. Talk to your doctor or genetic counselor if you have questions about testing for VLCADD.
CAN YOU TEST DURING A FUTURE PREGNANCY?
Yes, it is possible to test for VLCADD during pregnancy. The sample needed for this test is obtained by either CVS or amniocentesisThis 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 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 VLCADD. A genetic counselor can talk to you about your choices and answer other questions you may have about prenatal testing or testing your baby after birth.
CAN OTHER MEMBERS OF THE FAMILY HAVE VLCADD OR BE CARRIERS?
The brothers and sisters of a baby with VLCADD have a chance of being affected, even if they haven’t had symptoms. Finding out whether other children in the family have VLCADD is important because early treatment may prevent serious health problems. Talk to your doctor or genetic counselor about testing your other children for VLCADD.
Brothers and sisters who do not have VLCADD 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 VLCADD, your brothers and sisters have a 50% chance to be a VLCADD 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 VLCADD.
All states offer newborn screeningA 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. for VLCADD. However, when both parents are carriers, newborn screeningThe 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. results are not sufficient to rule out VLCADD in a newborn baby. In this case, special diagnostic testing should be done in addition to newborn screening.
During pregnancy, women carrying fetuses with VLCADD may be at increased risk to develop serious medical problems. A small number of women are known to have developed:
- excessive vomiting
- abdominal pain
- high blood pressure
- jaundiceThis is a yellow color to the skin and whites of the eyes. It is often a sign of liver damage.
- abnormal fat storage in the liver
- severe bleeding
All women with a family history of VLCADD should share this information with their obstetricians and other health care providers before and during any future pregnancies. Knowing about these risks allows early treatment.
CAN OTHER FAMILY MEMBERS BE TESTED?
Brothers and sisters of a child with VLCADD can have special testing to check for this disorder. Ask you metabolic doctor whether your other children should be tested for VLCADD.
Carrier testing may be available to other family members. Your metabolic doctor or genetic counselor can advise you about carrier testing.
HOW MANY PEOPLE HAVE VLCADD?
Originally thought to be rare, newborn screening has established that 1 in 30,000 to 100,000 people has VLCADD. Most people diagnosed with VLCADD through newborn screening do not have symptoms of VLCAD and are thought to have the childhood and adult types of VLCADD.
DOES VLCADD HAPPEN MORE OFTEN IN A CERTAIN ETHNIC GROUP?
No, VLCADD does not happen more often in any specific race, ethnic group, geographical area, or country.
DOES VLCADD GO BY ANY OTHER NAMES?
VLCADD is sometimes also called:
- VLCAD deficiency
- ACADVL deficiency
WHERE CAN I FIND MORE INFORMATION?
Fatty Oxidation Disorders (FOD) Family Support Group
Organic Acidemia Association
United Mitochondrial Disease Foundation
Metabolic Support UK
Baby’s First Test
Genetic Metabolic Dietitians International
|Reviewed by:||HI, CA, OR, and WA metabolic specialists|
|Review date:||April 4, 2011
July 13, 2013
May 18, 2020
March 1, 2023
|Update on:||May 18,2020|
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