Gene Tested



Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency


MCAD deficiency is a disorder of fatty acid oxidation that is inherited as an autosomal recessive disorder. This enzyme deficiency results in the inability to catabolize medium-chain (6-12 carbon molecules) fatty acids for energy utilization. MCAD deficiency often presents in the first two years of life after viral  illness or fasting. This inability to break down medium-chain lipids as an energy source during times of fasting and metabolic stress can result in hypoglycemia associated with vomiting, lethargy, apnea, coma, encephalopathy and sudden death. 


• Unexplained low blood sugars and metabolic acidosis in an infant 
• Abnormal newborn screen, organic acid profile, or acylcarnitine profile suggesting MCAD deficiency 

Testing Methodology 

• Genotyping for NM_000016.4: c.985A>G (K329E) allele only
•  PCR-based sequencing of entire coding region, intron/exon boundaries, as well as known pathogenic variants (HGMD 2017.3) in the promoter and deep intronic regions of the specified gene(s)

Sensitivity and Limitations

• Genotyping for c.985A>G (K329E)  allele: This test detects only the NM_000016.4: c.985A>G (K329E)  allele, which accounts for 50-68% of disease causing variants in ACADM. Heterozygous and normal test results may be reflexed to full gene sequencing, however an additional charge will apply.
• PCR-based sequencing detects >95% of variants in patients with MCAD deficiency. The analytical sensitivity of DNA sequencing is over 99% for the detection of nucleotide base changes, small deletions and insertions in the regions analyzed. Variants in regulatory regions and non-reported variants in untranslated regions may not be detected by this test. Large deletions/ duplications, large insertions and other complex genetic events will not be identified using sequencing methodology.

Turn-Around Time

• Genotyping for NM_000016.4: c.985A>G (K329E) allele: 2 business days
ACADM full gene sequence analysis: 14 days

CPT Codes

• Genotyping for NM_000016.4: c.985A>G (K329E) allele: 81400
ACADM full gene sequence analysis: 81479
ACADM family specific variant analysis: 81403

How to Order

Testing for this gene is also available as part the Metaboseq Gene Sequencing panel by next-generation sequencing. Deletion/duplication analysis and targeted variant analysis is also available for this gene. Download Inborn Errors of Metabolism requisition.


Bentler K., et al. (2016) 221 newborn-screened neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency: Findings from the Inborn Errors of Metabolism Collaborative. Mol Genet Metab. 2016 Sep;119(1-2):75-82.  

Gramer G., et al. (2015) Medium-Chain Acyl-CoA Dehydrogenase Deficiency: Evaluation of Genotype-Phenotype Correlation in Patients Detected by Newborn Screening. JIMD Rep. 2015;23:101-12. 

Kelly, D. P., J. J. Kim, et al. (1987). Nucleotide sequence of medium-chain acyl-CoA dehydrogenase mRNA and its expression in enzyme-deficient human tissue. Proc Natl Acad Sci U S A 84(12): 4068-4072.

Maier, E. M., B. Liebl, et al. (2005). Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency. Hum Mutat 25(5): 443-452.

Matern, D. and P. Rinaldo (2000; updated 2015). Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency. GeneReviews. R. A. Pagon, T. D. Bird, C. R. Dolan, K. Stephens and M. P. Adam. Seattle (WA).

Smith, E. H., C. Thomas, et al. (2010). Allelic diversity in MCAD deficiency: the biochemical classification of 54 variants identified during 5 years of ACADM sequencing. Mol Genet Metab 100(3): 241-250.

Zhang, Z. F., D. P. Kelly, et al. (1992). Structural organization and regulatory regions of the human medium-chain acyl-CoA dehydrogenase gene. Biochemistry 31(1): 81-89.