FATTY ACID DISORDER

Disorder name: Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Acronym: LCHADD
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• What is LCHADD?
• What causes LCHADD?
• If LCHADD is not treated, what problems occur?
• What is the treatment for LCHADD?
• What happens when LCHADD is treated?
• What causes the LCHAD enzyme to be absent or not working correctly?
• How is LCHADD inherited?
• Is genetic testing available?
• What other testing is available?
• Can you test during a future pregnancy?
• Can other members of the family have LCHADD or be carriers?
• Can other family members be tested?
• How many people have LCHADD?
• Does LCHADD happen more often in a certain ethnic group?
• Does LCHADD go by any other names?
• Where can I find more information?

This fact sheet contains general information about LCHADD. 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 LCHADD should be followed by a metabolic doctor in addition to their primary doctor.

WHAT IS LCHADD?

LCHADD stands for “long chain 3-hydroxyacyl-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 LCHADD have problems breaking down 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 LCHADD?

LCHADD is caused by problems with the enzyme “long chain 3-hydroxyacyl-CoA dehydrogenase” (LCHAD). In people with LCHADD, the LCHAD 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 LCHAD enzyme is missing or not working well, the body cannot break down fat for energy. Instead, it 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 LCHADD IS NOT TREATED, WHAT PROBLEMS OCCUR?

LCHADD can cause mild effects in some people and more serious health problems in others. Babies and children with LCHADD usually begin to show symptoms sometime from birth through age two. LCHADD causes episodes of hypoglycemia. The first symptoms of hypoglycemia are:

• extreme sleepiness or fatigueFatigue is a feeling of weariness, tiredness, or lack of energy. Fatigue can be a normal and important response to physical exertion, emotional stress, or lack of sleep. However, it can also be a sign of a more serious health disorder.
• weakness
• nausea
• vomiting
• irritability or jitteriness
• behavior changes

If hypoglycemia is not treated, a child with LCHADD can develop:

• breathing problems
• swelling of the brain
• 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

Symptoms often happen after having nothing to eat for more than a few hours. Symptoms are also more likely to occur when a person with LCHADD gets sick or has an infection.

Between episodes of hypoglycemia, people with LCHADD are usually healthy. However, repeated episodes can cause brain damage. This can result in learning problems or intellectual disabilities.

Babies and children who are not treated may have:

• poor weight gain
• delays in learning
• delays in walking and other motor skills
• enlarged liver and other liver problems
• enlarged heart and other heart problems
• vision loss due to build-up of pigment in the retina
• anemiaThis is a condition in which the blood has too few red blood cells or too little hemoglobin, the oxygen carrying molecule in the blood. People with anemia are often pale, tired, weak, dizzy and short of breath.
• nerve problems
• bouts of muscle weakness and pain, especially after heavy exercise or illness

Some children with LCHADD have never had symptoms and are only found to be affected after a brother or sister is diagnosed.

WHAT IS THE TREATMENT FOR LCHADD?

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 LCHADD.

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 LCHADD:

1. Avoid going a long time without food
Infants and young children with LCHADD need to eat frequently to prevent 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.. 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 LCHADD can go without food for up to 12 hours without problems. The other treatments usually need to be continued throughout life.

2.  Diet 
Sometimes a diet low in fat and high in carbohydrates 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 many types of sugar that can be used as energy. In fact, for children needing this treatment, most foods in the diet should be carbohydrates (bread, pasta, fruit, vegetables, etc.) and protein (lean meat and low-fat dairy foods). Any diet changes should be made under the guidance of a dietician familiar with LCHADD.

People with LCHADD 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 the fat in the diet will likely be in the form of 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..

Ask your doctor if your child needs to have any changes in his or her diet.

3.  Medium Chain Triglycerides
Medium Chain Triglycerides (MCT) are often used as part of the food plan for people with LCHADD. MCTs are available in MCT oil and in triheptanoin (DOJOLVI ®) – a medication made of MCTs. These supplements have 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. 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 L-carnitine. This is a safe and natural substance that helps body cellsThe 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. 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.

In addition to the above supplements, some doctors suggest taking docosahexanoic acid (DHA) which may help prevent loss of eyesight. Ask your doctor whether your child should use this supplement.

Do not use any supplements or medications 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
• vomiting
• diarrhea
• an infection
• a fever
• persistent muscle pain or weakness, or reddish-brown color to the urine

Children with LCHADD 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. Children who are sick often don’t want to eat. If they won’t or can’t eat, children with LCHADD may need to be treated in the hospital to prevent 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 heavy exercise can also trigger symptoms. Effects of exercise may include:

• muscle aches
• cramps
• weakness
• reddish-brown color to the urine (caused by breakdown of muscle fibers)

If muscle symptoms occur, prompt treatment is needed to prevent kidney damage. Children or 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 LCHADD IS TREATED?

With prompt and careful treatment, children with LCHADD can often live healthy lives with typical growth and development.

Even with treatment, some people with LCHADD continue to have episodes of hypoglycemia. This can lead to learning problems or intellectual disabilities. And, even with treatment, some people still develop vision, muscle, liver, or heart problems.

WHAT CAUSES THE LCHAD ENZYME TO BE ABSENT OR NOT WORKING CORRECTLY?

Genes tell the body to make various enzymes. The HADHA gene instructs the body to make the LCHAD enzyme. Everyone has two copies of the HADHA gene. People with LCHADD 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 HADHA 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 changes in this pair of genes, the LCHAD enzyme either does not work properly or is not made at all.

HOW IS LCHADD INHERITED?

LCHADD is inherited in an autosomal recessive manner. It affects both boys and girls equally.

Everyone has two copies of the HADHA gene that make the LCHAD enzyme. In children with LCHADD, neither of their HADHA genes works correctly. These children inherit one non-working HADHA gene for the condition from each parent.

Parents of children with LCHADD are rarely affected with the disorder. Instead, each parent has a single non-working gene for LCHADD. 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 LCHADD because their other HADHA gene is working correctly.

When both parents are carriers, there is a 25% chance in each pregnancy for the child to have LCHADD. 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 LCHADD. Genetic counselors can answer your questions about how LCHADD is inherited, choices 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 LCHADD can be done on a blood sample. Genetic testing, also called DNA testing, looks for changes (variants) in the pair of genes that causes LCHADD. About 70% of children with LCHADD have one particular change in both genes of this pair.

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 not necessary to diagnose your child. It can be helpful for carrier testing or prenatal diagnosis, discussed below.

WHAT OTHER TESTING IS AVAILABLE?

LCHADD can also be confirmed by a special test called a “fatty acid oxidation probe” using a skin sample. Talk to your doctor or your genetic counselor if you have questions about testing for LCHADD.

CAN YOU TEST DURING A FUTURE PREGNANCY?

If both gene changes (variants) have been found in your child with LCHADD, DNA testing can be done during future pregnancies. 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..

If DNA testing would not be helpful, testing during pregnancy can be done by a special test called a “fatty acid oxidation probe” using cells from the fetus. Again, the sample needed for this test is obtained by either CVSThis is a special test done early in pregnancy. During CVS, a small sample of the placenta is removed for testing. This sample can be used to test for certain genetic disorders in the fetus. CVS is usually done between 10 and 12 weeks of pregnancy. or 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 LCHADD. 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 LCHADD OR BE CARRIERS?

Having LCHADD
The brothers and sisters of a baby with LCHADD have a chance of being affected, even if they haven’t had symptoms. Finding out whether other children in the family have LCHADD is important because early treatment may prevent serious health problems. Talk to your doctor or genetic counselor about testing your other children for LCHADD.

LCHADD Carriers
Brothers and sisters who do not have LCHADD 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 LCHADD, your brothers and sisters have a 50% chance to be an LCHADD 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 LCHADD.

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 LCHADD. 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 LCHADD in a newborn baby. In this case, special diagnostic testing should be done in addition to newborn screening.

During pregnancy, women carrying fetuses with LCHADD are at risk to develop serious medical problems. Some of these women develop:

• 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 LCHADD 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?

Diagnostic testing
Brothers and sisters can be tested for LCHADD by DNA testing or other special tests to determine if they also have LCHADD.

Carrier testing
If both gene changes in the HADHA gene have been found in the child with LCHADD, other family members can have DNA testing to see if they are carriers.

HOW MANY PEOPLE HAVE LCHADD?

LCHADD is a rare disorder. It is estimated that 1 in 250,000 babies is born with LCHADD.

DOES LCHADD HAPPEN MORE OFTEN IN A CERTAIN ETHNIC GROUP?

Although LCHADD happens in every ethnic group, it happens more often in people who have ancestors from Estonia, Poland and Finland.

DOES LCHADD GO BY ANY OTHER NAMES?

LCHADD is also called:

• LCHAD deficiency
• 3hydroxyacyl-CoA dehydrogenase, long chain, deficiency
• Trifunctional proteinA 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. deficiency, type 1

A variant of LCHADD is called Trifunctional Protein Deficiency (TFP). Please see the TFP fact sheet for information on this condition.

WHERE CAN I FIND MORE INFORMATION?

Fatty Oxidation Disorders (FOD) Family Support Group
http://www.fodsupport.org

Organic Acidemia Association
http://www.oaanews.org

United Mitochondrial Disease Foundation
http://www.umdf.org

Metabolic Support UK
https://www.metabolicsupportuk.org/

Baby’s First Test
http://www.babysfirsttest.org

MedlinePlus
https://medlineplus.gov/genetics/condition/long-chain-3-hydroxyacyl-coa-dehydrogenase-deficiency/

DOCUMENT INFO:

Created by:	www.newbornscreening.info
Reviewed by:	HI, CA, OR, and WA metabolic specialists
Review date:	September 31, 2007 April 2, 2011 July 13, 2013 May 4, 2020 March 1, 2023
Update on:	March 1, 2023

DISCLAIMER:

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 MaternalHaving 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