eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Medium-Chain Acyl-CoA Dehydrogenase Deficiency: Differential Diagnoses & Workup

Author: Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Contributor Information and Disclosures

Updated: Sep 1, 2009

Workup

Laboratory Studies

  • Measurement of serum electrolyte levels may reveal depressed bicarbonate and an anion gap in medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) deficiency.
  • Blood glucose levels are low in asymptomatic individuals, although symptoms may be present prior to onset of hypoglycemia.
  • Blood ammonia levels may be mildly to moderately elevated.
  • Urinalysis is helpful in ruling out ketonuria; urine should be submitted for organic acid profile and acylcarnitine excretion pattern.

Other Tests

  • Molecular genetic testing can identify the nature of the mutation for purposes of prenatal diagnosis.

Histologic Findings

  • Liver tissue findings reveal large-droplet steatosis, electron-dense mitochondrial matrices, and increased width of the mitochondrial membrane. These changes are suggestive of a mitochondrial oxidative disorder but are not specific to MCAD deficiency.

More on Medium-Chain Acyl-CoA Dehydrogenase Deficiency

Overview: Medium-Chain Acyl-CoA Dehydrogenase Deficiency
Differential Diagnoses & Workup: Medium-Chain Acyl-CoA Dehydrogenase Deficiency
Treatment & Medication: Medium-Chain Acyl-CoA Dehydrogenase Deficiency
Follow-up: Medium-Chain Acyl-CoA Dehydrogenase Deficiency
Multimedia: Medium-Chain Acyl-CoA Dehydrogenase Deficiency
References
[ CLOSE WINDOW ]

References

  1. Gregersen N, Lauritzen R, Rasmussen K. Suberylglycine excretion in the urine from a patient with dicarboxylic aciduria. Clin Chim Acta. Aug 2 1976;70(3):417-25. [Medline].

  2. Gregersen N, Wintzensen H, Christensen SK, et al. C6-C10-dicarboxylic aciduria: investigations of a patient with riboflavin responsive multiple acyl-CoA dehydrogenation defects. Pediatr Res. Oct 1982;16(10):861-8. [Medline].

  3. Stanley CA, Hale DE, Coates PM, et al. Medium-chain acyl-CoA dehydrogenase deficiency in children with non- ketotic hypoglycemia and low carnitine levels. Pediatr Res. Nov 1983;17(11):877-84. [Medline].

  4. Maier EM, Liebl B, Roschinger W, et al. Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency. Hum Mutat. May 2005;25(5):443-52. [Medline].

  5. Maier EM, Gersting SW, Kemter KF, Jank JM, Reindl M, Messing DD. Protein misfolding is the molecular mechanism underlying MCADD identified in newborn screening. Hum Mol Genet. May 1 2009;18(9):1612-23. [Medline].

  6. Schuck PF, Ferreira GC, Moura AP, et al. Medium-chain fatty acids accumulating in MCAD deficiency elicit lipid and protein oxidative damage and decrease non-enzymatic antioxidant defenses in rat brain. Neurochem Int. Jul 2009;54(8):519-25. [Medline].

  7. Sauer SW, Okun JG, Hoffmann GF, Koelker S, Morath MA. Impact of short- and medium-chain organic acids, acylcarnitines, and acyl-CoAs on mitochondrial energy metabolism. Biochim Biophys Acta. Oct 2008;1777(10):1276-82. [Medline].

  8. Rhead WJ. Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: a global perspective. J Inherit Metab Dis. Apr-Jun 2006;29(2-3):370-7. [Medline].

  9. Waddell L, Wiley V, Carpenter K, et al. Medium-chain acyl-CoA dehydrogenase deficiency: genotype-biochemical phenotype correlations. Mol Genet Metab. Jan 2006;87(1):32-9. [Medline].

  10. Santos L, Patterson A, Moreea SM, et al. Acute liver failure in pregnancy associated with maternal MCAD deficiency. J Inherit Metab Dis. Feb 2007;30(1):103. [Medline].

  11. Huidekoper HH, Schneider J, Westphal T, et al. Prolonged moderate-intensity exercise without and with L-carnitine supplementation in patients with MCAD deficiency. J Inherit Metab Dis. Oct 2006;29(5):631-6. [Medline].

  12. Angelini C, Federico A, Reichmann H, Lombes A, Chinnery P, Turnbull D. Task force guidelines handbook: EFNS guidelines on diagnosis and management of fatty acid mitochondrial disorders. Eur J Neurol. Sep 2006;13(9):923-9. [Medline].

  13. Derks TG, Reijngoud DJ, Waterham HR, et al. The natural history of medium-chain acyl CoA dehydrogenase deficiency in the Netherlands: clinical presentation and outcome. J Pediatr. May 2006;148(5):665-670. [Medline].

  14. Derks TG, van Spronsen FJ, Rake JP, et al. Safe and unsafe duration of fasting for children with MCAD deficiency. Eur J Pediatr. Jan 2007;166(1):5-11. [Medline].

  15. DiMauro S, DiMauro PM. Muscle carnitine palmityltransferase deficiency and myoglobinuria. Science. Nov 20 1973;182(115):929-31. [Medline].

  16. Divry P, David M, Gregersen N, et al. Dicarboxylic aciduria due to medium chain acyl CoA dehydrogenase defect. A cause of hypoglycemia in childhood. Acta Paediatr Scand. Nov 1983;72(6):943-9. [Medline].

  17. Ensenauer R, Winters JL, Parton PA, et al. Genotypic differences of MCAD deficiency in the Asian population: novel genotype and clinical symptoms preceding newborn screening notification. Genet Med. May-Jun 2005;7(5):339-43. [Medline].

  18. Feillet F, Steinmann G, Vianey-Saban C, et al. Adult presentation of MCAD deficiency revealed by coma and severe arrythmias. Intensive Care Med. Sep 2003;29(9):1594-7. [Medline].

  19. Nennstiel-Ratzel U, Arenz S, Maier EM, et al. Reduced incidence of severe metabolic crisis or death in children with medium chain acyl-CoA dehydrogenase deficiency homozygous for c.985A>G identified by neonatal screening. Mol Genet Metab. Jun 2005;85(2):157-9. [Medline].

  20. Opdal SH, Rognum TO. The sudden infant death syndrome gene: does it exist?. Pediatrics. Oct 2004;114(4):e506-12. [Medline]. [Full Text].

  21. Raymond K, Bale AE, Barnes CA, Rinaldo P. Medium-chain acyl-CoA dehydrogenase deficiency: sudden and unexpected death of a 45 year old woman. Genet Med. Sep-Oct 1999;1(6):293-4. [Medline].

  22. Reis de Assis D, Maria Rde C, Borba Rosa R, et al. Inhibition of energy metabolism in cerebral cortex of young rats by the medium-chain fatty acids accumulating in MCAD deficiency. Brain Res. Dec 24 2004;1030(1):141-51. [Medline].

  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].

  25. Walter JH. L-carnitine in inborn errors of metabolism: what is the evidence?. J Inherit Metab Dis. 2003;26(2-3):181-8. [Medline].

  26. Wang SS, Fernhoff PM, Hannon WH, Khoury MJ. Medium chain acyl-CoA dehydrogenase deficiency human genome epidemiology review. Genet Med. Nov-Dec 1999;1(7):332-9. [Medline].

  27. Wilhelm GW. Sudden death in a young woman from medium chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. J Emerg Med. Apr 2006;30(3):291-4. [Medline].

  28. Yang W, Roth KS, Coates PM. Hypoglycemic, hypoketotic dicarboxylic aciduria--a possible defect in fatty acid oxidation (Abstract). Pediatr Res. 1982;16(4):267A.

  29. Ziadeh R, Hoffman EP, Finegold DN, et al. Medium chain acyl-CoA dehydrogenase deficiency in Pennsylvania: neonatal screening shows high incidence and unexpected mutation frequencies. Pediatr Res. May 1995;37(5):675-8. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

medium-chain acyl-coenzyme A dehydrogenase deficiency, medium-chain acyl-CoA dehydrogenase deficiency, MCAD deficiency, medium-chain dicarboxylic aciduria, inborn error of metabolism, beta-oxidation cycle, carnitine palmitoyltransferase deficiency, CPT deficiency, Reye syndrome, fatty acid metabolism, hypoglycemia, hypoketonuria, exaggerated lethargy

[ CLOSE WINDOW ]

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: MDS Pharma Salary Employment

Medical Editor

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

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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

CME Editor

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, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, 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.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.