Medium-Chain Acyl-CoA Dehydrogenase Deficiency Clinical Presentation

  • Author: Karl S Roth, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Apr 13, 2012
 

History

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

  • 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.
  • 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.
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Causes

  • The gene has been mapped to locus 1p31; several allelic variations have been reported. 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.[9] 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.[10]
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Contributor Information and Disclosures
Author

Karl S Roth, MD  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 Clinical 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, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

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, American Society of Gene Therapy, American Society of Human Genetics, Child Neurology Society, and Society for Inherited Metabolic Disorders

Disclosure: Genzyme Corporation Salary Management position

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, New York

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

Disclosure: Genzyme Grant/research funds PI

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

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  23. Tajima G, Sakura N, Yofune H, et al. Enzymatic diagnosis of medium-chain acyl-CoA dehydrogenase deficiency by detecting 2-octenoyl-CoA production using high-performance liquid chromatography: a practical confirmatory test for tandem mass spectrometry newborn screening in Japan. J Chromatogr B Analyt Technol Biomed Life Sci. Sep 5 2005;823(2):122-30. [Medline].

  24. Van Hove JL, Zhang W, Kahler SG, et al. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: diagnosis by acylcarnitine analysis in blood. Am J Hum Genet. May 1993;52(5):958-66. [Medline].

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Autosomal recessive inheritance.
 
 
 
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