Very Long Chain Acyl-CoA Dehydrogenase Deficiency, Known Mutation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive disorder of mitochondrial fatty acid beta-oxidation. Mitochondrial beta-oxidation plays a major role in energy production and VLCAD catalyzes the first step in the breakdown of fatty acids that are 14 to 20 carbons long.
VLCAD deficiency has a reported incidence of approximately 1 in 30,000 births and has a variable age of onset that is generally classified into 3 categories. Individuals with the early-onset type present with cardiomyopathy, hypotonia, and hepatomegaly in the first months of life; sudden death is also frequent. Individuals with the early-childhood onset type typically present with hypoketotic hypoglycemia and hepatomegaly without cardiomyopathy. Individuals with the late-onset type of VLCAD deficiency generally present after childhood with intermittent rhabdomyolysis and muscle dysfunction that often manifests as muscle cramps and exercise intolerance.
Review of clinical features and biochemical analysis via plasma acylcarnitines, plasma fatty acid profile, urine organic acids, and fibroblast fatty acid oxidation probe studies are recommended as laboratory evaluations for VLCAD deficiency. Plasma and urine biochemical testing are not reliable for identifying all individuals with VLCAD deficiency or confirming carrier status, as biochemical findings may normalize during periods of good metabolic control. It is uncertain whether skin fibroblast analysis can identify carriers of VLCAD deficiency. The diagnosis is confirmed by molecular testing.
Mutations in the ACADVL gene are responsible for VLCAD deficiency. Most mutations are family specific with the exception of the V283A mutation (also reported in the literature as V243A). This mutation is estimated to account for 20% of pathogenic alleles in patients identified by newborn screening. When this test is ordered, results of biochemical assays should be included with the specimen as they are necessary for accurate interpretation of the VLCAD sequence analysis.
Diagnostic confirmation of very long chain acyl-CoA dehydrogenase (VLCAD) deficiency when familial mutations have been previously identified
Carrier screening of at-risk individuals when a mutation in the ACADVL gene has been identified in an affected family member
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order VLCMS/60036 Very Long Chain Acyl-CoA Dehydrogenase Deficiency, Full Gene Analysis.
Analysis is performed for the familial mutation(s) provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with metabolic disease.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Andresen BS, Olpin S, Poorthuis BJ, et al: Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency. Am J Hum Genet 1999;64:479-494
2. Liebig M, Schymik I, Mueller M, et al: Neonatal screening for very long-chain acyl-CoA dehydrogenase deficiency: enzymatic and molecular evaluation of neonates with elevated C14:1-carnitine levels. Pediatrics 2006;118:1065-1069