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Medium-Chain Acyl-CoA Dehydrogenase Deficiency Clinical Presentation

  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD  more...
Updated: Aug 17, 2015


Because medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive trait, other affected members of a family pedigree are unlikely to be historically available to assist in diagnosis.

The naturally frequent feeding of a very young infant tends to offset the need for reliance on alternative fuel for fasting; however, as the infant begins to extend the interval between feedings, the need for fatty acid catabolism correspondingly increases. Historically, this need may correlate with increased preprandial irritability, lethargy, jitteriness, sweating, and, possibly, seizures, which are all symptomatic of hypoglycemia.

Exaggerated lethargy accompanied by vomiting and acidosis with previous viral illness, often requiring intravenous fluid replacement therapy, is common.

Although early development is usually normal, growth may be somewhat slow.



Prior to acute clinical presentation, physical examination findings may be entirely normal or may be remarkable only for a growth rate below the reference range.

Upon acute presentation, the infant is likely to be tachypneic, somnolent, and have a mildly enlarged liver, which is due to fatty infiltration. Hepatomegaly is a cardinal feature of MCAD, as well as of other fatty acid oxidative disorders.[14]

Neurological examination is nonspecific, without localizing signs.

If the infant has experienced a hypoglycemic seizure, distinguishing a postictal state from coma due to cerebral edema is vital.

The adult presentation may be characterized by headaches and vomiting, probably relating to hyperammonemia and to the cerebral metabolic effects of accumulated octanoate.



The gene has been mapped to locus 1p31; more than 80 allelic variations have been reported.[15] The most common mutation is 985A>G, which refers to a substitution of a guanine nucleotide for an adenine nucleotide at the 985th residue. A second mutation, 583G>A, is reportedly common in certain populations. One study reported that individuals homozygous for 985A>G or 583G>A mutations had the highest levels of octanoylcarnitine, even when asymptomatic, and had the most severe clinical manifestations.[16] This has not been confirmed to date.

Phenotype-genotype relationships have been sought, with little success. As an example, although the common 985A>G mutation is frequently responsible for infantile onset, the same mutation has been reported in a patient with adult onset.

Acute hepatic failure in a previously healthy gravid female who is homozygous for the 985A>G mutation has been reported, thus confirming the potential for later onset, as well as the severity of complications with this specific mutation.[17]

Contributor Information and Disclosures

Karl S Roth, MD Retired Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Edward Kaye, MD Vice President of Clinical Research, Genzyme Corporation

Edward Kaye, MD is a member of the following medical societies: American Academy of Neurology, Society for Inherited Metabolic Disorders, American Society of Gene and Cell Therapy, American Society of Human Genetics, Child Neurology Society

Disclosure: Received salary from Genzyme Corporation for management position.

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Autosomal recessive inheritance.
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