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Genetic and Rare Diseases Information Center (GARD)

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Medium-chain acyl-coenzyme A dehydrogenase deficiency


Other Names for this Disease

  • ACADM deficiency
  • Acyl-CoA dehydrogenase medium chain deficiency of
  • MCAD deficiency
  • MCADD
  • MCADH deficiency
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

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?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency?

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). Normally, through a process called fatty acid oxidation, several enzymes work in a step-wise fashion to break down (metabolize) fats and convert them to energy. People with MCADD do not have enough of an enzyme needed for the step that metabolizes a group of fats called medium-chain fatty acids. MCADD is caused by mutations in the ACADM gene and is inherited in an autosomal recessive manner.[1] Treatment includes avoidance of fasting and of medium chain triglycerides in the diet.[2]
Last updated: 7/7/2014

What are the signs and symptoms of medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency?

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: 7/7/2014

How is medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) diagnosed?

MCADD is now included in many newborn screening programs. If a newborn screening result for MCADD is not in the normal range, additional testing is recommended. A diagnosis of MCADD can be made through a blood test called a plasma acylcarnitine profile and an evaluation of organic acids in the urine. The diagnosis can also be confirmed by genetic testing.[2]
Last updated: 7/7/2014

What is newborn screening?

Newborn screening tests look for serious developmental, genetic, and metabolic disorders so that important action can be taken during the critical time before symptoms develop. Screening tests do not diagnose illnesses. They identify which babies need additional testing to confirm or rule out illnesses. Good screening tests have a low false-negative rate (if the test is normal, the child should be healthy), but may have a high false-positive rate (as many affected children as possible should test positive, even if this means many healthy children also test positive).[3]

An abnormal result on a newborn screen means that the child should have additional testing to confirm or rule out the condition. If a disorder is diagnosed on follow-up testing, appropriate treatment can be started right away, before symptoms appear.[3]

Last updated: 11/10/2008

Are there factors which can cause a false positive test result for medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency on newborn screen?

The false positive rate for medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency varies between screening programs because of differences in acylcarnitine analysis and profiling. Programs that screen for MCAD deficiency but not other fatty acid oxidation disorders often limit their analysis to octanoylcarnitine, the predominant marker for MCAD deficiency. However, octanoylcarnitine is not specific for MCAD deficiency and is expected to be elevated in several other disorders (i.e., medium-/short-chain 3-hydroxy acyl-CoA dehydrogenase deficiency, medium-chain 3-keto acyl-CoA thiolase deficiency, glutaric acidemia type II) and in newborns treated with valproate or fed a diet rich in medium-chain triglycerides. Consideration disorders included in the differential diagnosis should minimize the false positive rate.[4]

Last updated: 11/10/2008

What follow-up testing can be done to definitively determine if my child has medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency?

ACADM is the only gene known to be associated with medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. The biochemical diagnosis of MCAD deficiency can be confirmed by measurement of MCAD enzyme activity in fibroblasts or other tissues and/or by molecular genetic testing of the ACADM gene. Both mutation analysis for the common K304E allele and sequence analysis to detect rarer alleles are available on a clinical basis.[4]

Follow-up testing can be ordered by your daughter's pediatrician or through a genetics clinic. Genetics clinics are a source of information for individuals and families regarding genetic diagnosis, natural history, treatment, mode of inheritance, and genetic risks to other family members. To find a genetics clinic, we recommend that you contact your primary doctor for a referral. Click here to learn more about genetic consultations. 

The following online resources can also help you find a genetics professional in your community:

  * GeneTests - A searchable directory of US and international genetics and prenatal diagnosis clinics. Go to the following link and click on 'Clinic Directory' to find a genetic service close to you.
http://www.geneclinics.org/

  * ResourceLink - A database of genetics counseling services, searchable by location, name, institution, type of practice, or specialty. Hosted by the National Society of Genetic Counselors.
http://www.nsgc.org/resourcelink.cfm

  * Genetic Centers, Clinics, and Departments - A comprehensive resource list for genetic counseling, including links to genetic centers and clinics, associations, and university genetics departments. Hosted by the University of Kansas Medical Center.
http://www.kumc.edu/gec/prof/genecntr.html

Last updated: 11/10/2008

References
Other Names for this Disease
  • ACADM deficiency
  • Acyl-CoA dehydrogenase medium chain deficiency of
  • MCAD deficiency
  • MCADD
  • MCADH deficiency
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.