VLCAD deficiency is inherited in an autosomal recessive pattern. Normally a person has two functional ACADVL genes. In people with VLCAD deficiency, both genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with VLCAD deficiency typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
Carriers of VLCAD deficiency do not typically have symptoms.
There are three types of VLCAD deficiency, which are all caused by mutations in the ACADVL gene. Symptoms of the most severe type typically begin in infancy and include cardiac (heart) symptoms (cardiomyopathy, arrhythmias), hypotonia (low muscle tone), hepatomegaly (enlarged liver) and intermittent hypoglycemia (low blood sugar). The second type has a childhood onset and symptoms may be similar to the infantile onset excluding cardiac symptoms. The third type has a later onset and episodes of rhabdomyolysis (breakdown of muscle fibers), muscle cramps and exercise intolerance.
- Incidence: The overall incidence is approximately 1 in 30,000.
- New York State Method of Screening (First Tier): Screening for VLCAD deficiency is accomplished by measuring acylcarnitines (C14 and C14:1) by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: Screening may be normal in patients with mild VLCAD deficiency who were recently fed, who received IV glucose or who were not ill when the specimen was collected.
- Interpretation/reporting of data: Results are reported as screen negative or as a referral. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for VLCAD deficiency are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of VLCAD deficiency.
Diagnostic testing may include quantification of plasma acylcarnitines, molecular genetic testing of the ACADVL gene, functional analysis of fatty acid oxidation on fibroblasts (skin cells), enzyme analysis on fibroblasts or enzyme analysis on lymphocytes.
Treatment is dietary including avoidance of fasting, drinking low-fat formula and supplementation with medium-chain triglycerides (MCT) as a source of supplemental calories. Treatment for cardiac involvement or rhabdomyolysis is supportive.
Prognosis is variable and dependent on multiple factors including the severity of disease and response to treatments.
Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a fatty acid oxidation disorder (inherited metabolic disorder).
VLCAD deficiency is caused by mutations in the ACADVL gene. Individuals with this disorder are unable to convert certain fats to energy and may develop symptoms during times of high energy need such as when fasting or ill.