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Medium-chain acyl-coenzyme A dehydrogenase deficiency


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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


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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


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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.

Showing of 44 |
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: 1/1/2021
Do you have updated information on this disease? We want to hear from you.

Cause Cause


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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


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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


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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


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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


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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 DocSM is for informational and educational purposes only.

Related Diseases Related Diseases


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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


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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


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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


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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


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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


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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


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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


  1. Medium-chain acyl-coenzyme A dehydrogenase deficiency. Genetics Home Reference (GHR). February, 2015; http://ghr.nlm.nih.gov/condition=mediumchainacylcoenzymeadehydrogenasedeficiency.
  2. 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.
  3. 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? We want to hear from you.
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