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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
  • MCADH deficiency
More Names
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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 (MCAD) deficiency is an inherited metabolic condition 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 MCAD deficiency have inadequate levels of an enzyme required for the step that metabolizes a group of fats called medium-chain fatty acids. Mutations in the ACADM gene cause MCAD deficiency.[1]
Last updated: 2/4/2011

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 (MCAD) deficiency 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 MCAD deficiency occurs during adulthood. People with this disorder are also at risk of serious complications such as seizures, breathing difficulties, liver problems, brain damage, coma, and sudden unexpected death.[1]

The signs and symptoms of MCAD deficiency can be triggered by periods of fasting or illnesses such as viral infections, particularly when eating is reduced.[1] 

Last updated: 2/4/2011

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

Diagnosis of medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency requires the integrated interpretation of multiple analyses, including consideration of the clinical status of the affected individual (i.e., acutely symptomatic vs. asymptomatic) at the time of sample collection. Initial testing should include the following analyses and their proper interpretation: plasma acylcarnitines, plasma fatty acid (free or total) profile, urine organic acids, and urine acylglycines. 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.[2]
Last updated: 2/4/2011

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.[2]

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.[2]

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.

  * 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.

  * 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.

Last updated: 11/10/2008