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

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Autosomal recessive inheritance	-
Cerebral edema	-
Coma	-
Decreased plasma carnitine	-
Elevated hepatic transaminases	-
Hepatic steatosis	-
Hepatomegaly	-
Hyperglycinuria	-
Hypoglycemia	-
Lethargy	-
Medium chain dicarboxylic aciduria	-
Muscular hypotonia	-
Seizures	-
Vomiting	-

Last updated: 10/1/2017

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

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.
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.

Do you have updated information on this condition? Let us know.

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

Children Living with Inherited Metabolic Diseases (CLIMB)
Climb Building
176 Nantwich Road
Crewe CW2 6BG
United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: contact@climb.org.uk
Website: http://www.climb.org.uk
FOD (Fatty Oxidation Disorder) Family Support Group
P.O. Box 54
Okemos, MI 48805-0054
Telephone: 517-381-1940
Fax: 866-290-5206
E-mail: deb@fodsupport.org
Website: http://www.fodsupport.org
Genetic Metabolic Dietitians International
P.O. Box 33985
Fort Worth, TX 76162
Website: http://www.gmdi.org/
MitoAction
PO Box 51474
Boston, MA 02205
Toll-free: 888-648-6228
Telephone: 1-888-MITO-411 (648-6411) for support line
E-mail: info@mitoaction.org
Website: http://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: 888-317-8633
Telephone: 412-793-8077
Fax: 412-793-6477
E-mail: info@umdf.org
Website: http://www.umdf.org

Do you know of an organization? Send us your suggestions.

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.

Healthcare Resources

You can submit a question to Ask the Mito Doc^SM , a service of the United Mitochondrial Diseases Foundation. Information contained in Ask the Mito Doc^SM is for informational and educational purposes only.

Genetics 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 GeneTests, 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.

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

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

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

Other Conferences

The International Network for Fatty Acid Oxidation Research and Management (INFORM) has been formed in order to promote research and discussion into the cause, diagnosis, and management of inborn errors of fatty acid oxidation. INFORM will sponsor an inaugural symposium to be held on September 6, 2014 in Innsbruck, Austria following SSIEM, with annual meetings thereafter. The Network will provide a collaborative framework for ongoing communication and research between the members.

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/.

Do you know of a review article? Send us your suggestions.