Gene Tested

ACADVL

Disease

Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency

Description

VLCAD deficiency is a disorder of fatty acid metabolism that is inherited as an autosomal recessive disorder.  This enzyme deficiency results in the inability to catabolize C10-C18 or longer straight-chain fatty acids for energy utilization. VLCAD deficiency may present in the first two years of life after illness or fasting. This inability to break down long chain fatty acids may result in hypoglycemia, lethargy, muscle weakness, cardiomyopathy, and liver disease especially in infants often leading to death. A milder, late-onset form that occurs in older children or adults may present with muscle soreness and exercise-induced rhabdomyolysis.

Indications

Cardiomyopathy, pericardial effusion, and/or arrhythmia
Hypoglycemia
Rhabdomyolysis/skeletal myopathy
Abnormal newborn screen or acylcarnitine profile suggesting VLCAD deficiency

Testing Methodology 

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

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

7-14 days

CPT Codes

ACADVL full gene sequence analysis: 81406
ACADVL 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.

References

Andresen, B. S., S. Olpin, et al. (1999). Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency. Am J Hum Genet 64(2): 479-494.

Boneh, A., B. S. Andresen, et al. (2006). VLCAD deficiency: pitfalls in newborn screening and confirmation of diagnosis by mutation analysis. Mol Genet Metab 88(2): 166-170.

Laforet, P., C. Acquaviva-Bourdain, et al. (2009). Diagnostic assessment and long-term follow-up of 13 patients with Very Long-Chain Acyl-Coenzyme A dehydrogenase (VLCAD) deficiency. Neuromuscul Disord 19(5): 324-329.

Leslie, N. D., B. T. Tinkle, et al. (2009; updated 2018). Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency. GeneReviews. R. A. Pagon, T. D. Bird, C. R. Dolan, K. Stephens and M. P. Adam. Seattle (WA).

Mathur, A., H. F. Sims, et al. (1999). Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death. Circulation 99(10): 1337-1343.

Miller MJ., et al. (2015) Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States. Mol Genet Metab. 2015 Nov;116(3):139-45.  

Schiff M., et al. (2013) Molecular and cellular pathology of very-long-chain acyl-CoA dehydrogenase deficiency. Mol Genet Metab. 2013 May;109(1):21-7.