Medium-chain acyl-coenzyme A dehydrogenase deficiency

Title

Other Names:

MCAD deficiency; Acyl-CoA dehydrogenase medium chain deficiency of; MCADH deficiency; MCAD deficiency; Acyl-CoA dehydrogenase medium chain deficiency of; MCADH deficiency; ACADM deficiency; MCADD; Medium chain acyl CoA dehydrogenase deficiency; Medium-chain acyl-CoA dehydrogenase deficiency See More

Categories:

Congenital and Genetic Diseases; Metabolic disorders; Newborn Screening

Summary Summary

Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is an inherited metabolic disorder that prevents the body from converting certain fats to energy, particularly during periods without food (fasting). People with MCADD do not have enough of an enzyme needed to metabolize a group of fats called medium-chain fatty acids. Signs and symptoms usually begin by early childhood and may include vomiting, lack of energy, and low blood sugar (hypoglycemia). Symptoms can be triggered by periods of fasting or by illnesses.^[1]

MCADD is caused by mutations in the ACADM gene and inheritance is autosomal recessive.^[1] Treatment includes strict avoidance of fasting and avoidance of medium chain triglycerides in the diet.^[2] If not treated, people with MCADD are at risk of serious complications including sudden death.^[1]

Last updated: 8/29/2017

Symptoms Symptoms

The initial signs and symptoms of medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) typically occur during infancy or early childhood and can include vomiting, lack of energy (lethargy), and low blood sugar (hypoglycemia). In rare cases, the first episode of problems related to MCADD occurs during adulthood. The signs and symptoms of MCADD can be triggered by periods of fasting, or during illnesses such as viral infections, particularly when eating is reduced. People with MCADD are also at risk of serious complications such as seizures, breathing difficulties, liver problems, brain damage, coma, and sudden, unexpected death.^[1]

Last updated: 8/29/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
30%-79% of people have these symptoms
Decreased liver function	Liver dysfunction	0001410
Decreased plasma total carnitine		0011936
Dicarboxylic aciduria		0003215
Exercise-induced myalgia	Exercise-induced muscle pain Muscle pain on exercise Muscle pain with exercise Muscle pain, exercise-induced [ more ]	0003738
Fatigable weakness of neck muscles		0030199
Hepatomegaly	Enlarged liver	0002240
Hyperammonemia	High blood ammonia levels	0001987
Muscular hypotonia	Low or weak muscle tone	0001252
Proximal muscle weakness	Weakness in muscles of upper arms and upper legs	0003701
Reduced tendon reflexes		0001315
Vomiting	Throwing up	0002013
5%-29% of people have these symptoms
Abnormal lactate dehydrogenase level		0045040
Arrhythmia	Abnormal heart rate Heart rhythm disorders Irregular heart beat Irregular heartbeat [ more ]	0011675
Ataxia		0001251
Bilateral tonic-clonic seizure	Grand mal seizures	0002069
Cachexia	Wasting syndrome	0004326
Cardiomegaly	Enlarged heart Increased heart size [ more ]	0001640
Coma		0001259
Delayed speech and language development	Deficiency of speech development Delayed language development Delayed speech Delayed speech acquisition Delayed speech development Impaired speech and language development Impaired speech development Language delay Language delayed Language development deficit Late-onset speech development Poor language development Speech and language delay Speech and language difficulties Speech delay [ more ]	0000750
Diarrhea	Watery stool	0002014
Distal arthrogryposis		0005684
Elevated hepatic transaminase	High liver enzymes	0002910
Elevated serum creatine kinase	Elevated blood creatine phosphokinase Elevated circulating creatine phosphokinase Elevated creatine kinase Elevated serum CPK Elevated serum creatine phosphokinase High serum creatine kinase Increased CPK Increased creatine kinase Increased creatine phosphokinase Increased serum CK Increased serum creatine kinase Increased serum creatine phosphokinase [ more ]	0003236
Elevated urinary 3-hydroxybutyric acid		0040155
Exertional dyspnea		0002875
Fatigue	Tired Tiredness [ more ]	0012378
Febrile seizure (within the age range of 3 months to 6 years)	Fever induced seizures	0002373
Hepatic steatosis	Fatty infiltration of liver Fatty liver [ more ]	0001397
Hypoglycemia	Low blood sugar	0001943
Ketosis	High levels of ketone bodies	0001946
Lethargy		0001254
Loss of consciousness	Passing out	0007185
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Muscle spasm		0003394
Myopathy	Muscle tissue disease	0003198
Skeletal muscle atrophy	Muscle degeneration Muscle wasting [ more ]	0003202
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance		0000007
Cerebral edema	Swelling of brain	0002181
Decreased plasma carnitine		0003234
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Global developmental delay		0001263
Hyperglycinuria	High urine glycine levels	0003108
Medium chain dicarboxylic aciduria		0008309
Seizure		0001250

Showing of 44 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 9/1/2020

Do you have updated information on this disease? We want to hear from you.

Cause Cause

MCADD is caused by mutations in the ACADM gene. This gene gives the body instructions for making an enzyme called medium-chain acyl-CoA dehydrogenase, needed to break down fats called medium-chain fatty acids. These fatty acids are found in foods and the body's tissues, and are an important source of energy for the heart, muscles, liver, and other tissues. Mutations in this gene lead to low levels of the enzyme, which means that medium-chain fatty acids are not broken down properly. They cannot be converted to energy, leading to the symptoms of MCADD.^[1]

Last updated: 8/29/2017

Inheritance Inheritance

Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is inherited in an autosomal recessive manner.^[1] This means that to have MCADD, a person must have a mutation in both copies of the responsible gene in each cell. There is nothing either parent can do, before or during a pregnancy, to cause a child to have this condition.

People with MCADD inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

25% chance to have the condition
50% chance to be an unaffected carrier like each parent
25% chance to be unaffected and not a carrier

Last updated: 8/29/2017

Diagnosis Diagnosis

A diagnosis of MCADD requires an evaluation of a person's symptoms as well as the interpretation of several tests. Initial testing may include:

Plasma acylcarnitine
Urine organic acid
Urine acylglycine

Further testing to confirm the diagnosis may include molecular genetic testing of the ACADM gene or biochemical genetic testing.^[3]

MCADD is included in many newborn screening programs, so a newborn with MCADD who does not yet exhibit symptoms may be diagnosed early. If a newborn screening result for MCADD is not in the normal range ("positive"), additional testing can then be ordered.^[2]

Last updated: 8/29/2017

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Orphanet lists international laboratories offering diagnostic testing for this condition.

Newborn Screening

An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

Genetic Metabolic Dietitians International (GMDI) has developed nutrition guidelines for this condition.
Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.
You can submit a question to Ask the Mito Doc, a service of the United Mitochondrial Diseases Foundation. Information contained in Ask the Mito Doc^SM is for informational and educational purposes only.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes other disorders of mitochondrial fatty acid oxidation including multiple acyl-CoA dehydrogenase deficiency (MADD) (see this term). Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.
The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

FOD (Fatty Oxidation Disorder) Family Support Group
P.O. Box 54
Okemos, MI 48805-0054
Telephone: +1-517-381-1940 [8am - 8pm EST every day]
Fax: +1-866-290-5206
E-mail: deb@fodsupport.org
Website: https://fodsupport.org/
Genetic Metabolic Dietitians International
P.O. Box 1462
Hillsborough, NC 27278
E-mail: info@gdmi.org
Website: http://www.gmdi.org/
Metabolic Support UK
5 Hilliards Court
Sandpiper Way
Chester Business Park
Chester, CH4 9QP United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: https://www.metabolicsupportuk.org/contact-us
Website: https://www.metabolicsupportuk.org
MitoAction
PO Box 51474
Boston, MA 02205
Toll-free: 1-888-648-6228
Telephone: 1-888-MITO-411 (648-6411) for support line
E-mail: info@mitoaction.org
Website: https://www.mitoaction.org/
Organic Acidemia Association
9040 Duluth Street
Golden Valley, MN 55427
Telephone: 763-559-1797
Fax: 866-539-4060
E-mail: mkstagni@gmail.com
Website: http://www.oaanews.org/
United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
Toll-free: 1-888-317-8633
Telephone: +1-412-793-8077
Fax: +1-412-793-6477
E-mail: info@umdf.org
Website: https://www.umdf.org

Do you know of an organization? We want to hear from you.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Education Resources

The Genetics Education Materials for School Success (GEMSS) aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Medium-chain acyl-coenzyme A dehydrogenase deficiency. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Medium-chain acyl-coenzyme A dehydrogenase deficiency. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Wang, et al. Is the G985A Allelic Variant of Medium-Chain Acyl-CoA Dehydrogenase a Risk Factor for Sudden Infant Death Syndrome? A Pooled Analysis. Pediatrics. 2000;105:1175-1176.

News & Events News & Events

News

Rare Diseases Are Not Rare - Gallery of Creative Work Raises Awareness of Rare Diseases
September 1, 2020
NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
NCATS Translational Approach Addresses COVID-19
May 21, 2020

Other Conferences

The International Network for Fatty Acid Oxidation Research and Management (INFORM) was formed in order to promote research and discussion into the cause, diagnosis, and management of fatty acid oxidation disorders (FAODs). They offer several learning opportunities throughout the year for patients, families, and researchers. INFORM's Annual Meeting will be held on August 30th and 31st, 2020 in Freiberg, Germany preceding the Society for the Study of Inborn Errors of Metabolism (SSIEM). The Network also continues to provide a collaborative framework for ongoing communication and research regarding FAODs.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I am wondering if there is any information about children suffering from MCADD experiencing white stools for any reason related to the metabolic disorder. Is this a sign that my daughter is getting fat build-up on her heart, brain, or liver? Please let me know what you think. See answer
My daughter was diagnosed with medium-chain acyl-coenzyme A dehydrogenase deficiency at 2 weeks. She is now 10 weeks old and seems to eat a lot. She's having breast and bottle milk but can drink 80z of hungry baby formula. Is it normal for her to be hungry all the time? Also, what happens to the fats as she can't break them down further? See answer
I have two sons with MCAD deficiency. I was recently told by the doctor that my sons will not be able to consume any alcohol when old enough to do so because it could lead to death. I would really like more information on this. See answer
My sister's daughter (my niece) recently had a baby and he was diagnosed with medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. If this condition is traced back to my sister, is it important for me and/or my children (ages 8 and 11) to be tested? See answer
My daughter had newborn screening performed at the hospital after her birth. Her doctor recently called to tell us that her test came back abnormal for medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. Are there factors that may contribute to a falsely positive result? See answer

Have a question? Contact a GARD Information Specialist.

References References

Medium-chain acyl-coenzyme A dehydrogenase deficiency. Genetics Home Reference (GHR). February, 2015; http://ghr.nlm.nih.gov/condition=mediumchainacylcoenzymeadehydrogenasedeficiency.
Simon Olpin. Medium chain acyl-CoA dehydrogenase deficiency. Orphanet. February, 2014; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=42.
Matern D, Rinaldo P. Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency. GeneReviews. March 5, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1424/.

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