Rare Infectious Disease News

Disease Profile

Medium-chain acyl-coenzyme A dehydrogenase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

E71.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

MCAD deficiency; Acyl-CoA dehydrogenase medium chain deficiency of; MCADH deficiency;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Newborn Screening

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]

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]

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.

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

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]

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]

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

      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

        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

          Organizations Providing General Support

            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.

                References

                1. Medium-chain acyl-coenzyme A dehydrogenase deficiency. Genetics Home Reference (GHR). February, 2015; https://ghr.nlm.nih.gov/condition=mediumchainacylcoenzymeadehydrogenasedeficiency.
                2. Simon Olpin. Medium chain acyl-CoA dehydrogenase deficiency. Orphanet. February, 2014; https://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/.

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