VLCADD - Description

Other Names

VLCADD, VLCAD deficiency, Very long chain acyl-CoA dehydrogenase deficiency, ACADVL deficiency

ICD-9

277.85, disorders of fatty acid oxidation

The ICD-9-CM code 277.85 includes several disorders of fatty acid oxidation, of which VLCADD is one. Also see VLCADD ICD9 (PDF Document 55 KB) for codes for related complications.

Description

Very long chain acyl-CoA dehydrogenase deficiency (VLCADD) is a disorder of fatty acid oxidation. During times of fasting, the body uses fats as a major source of energy, breaking them down through a process called beta-oxidation. This process involves several enzymes that break down very-long chain fats to long-chain fats and long-chain fats to medium-chain fats, eventually resulting in ketone bodies and acetyl-CoA. The former are used directly for energy and the latter enter the Kreb cycle to generate ATP and reducing equivalents. Very long chain acyl-CoA dehydrogenase is needed to break down and use fats with large numbers of carbons (14-20). Because these fatty acids, which are the most abundant fats in the human body, are generally used during prolonged fasting and/or periods of increased energy demands (fever, stress, infections), these conditions often precipitate manifestations of VLCADD – energy production is impaired, leading to hypoglycemia and lethargy, and fatty acids that are not broken down accumulate in cells, causing metabolic crisis, cardiac arrhythmia, cardiomyopathy, muscle pain, and/or myoglobinuria.

VLCADD is clinically heterogeneous, with three major phenotypes based on varying degrees of enzyme deficiency. The early onset (infantile) form, associated with nearly complete absence of the enzyme, is characterized by dilated or hypertrophic cardiomyopathy, arrhythmia, hypotonia, hepatomegaly, hypoglycemia, and high morbidity and mortality, usually shortly after birth. The childhood form is milder, with hypoketotic hypoglycemia, similar to MCAD deficiency with increased values of liver function tests and elevated creatine kinase. Symptoms are usually triggered by stress and cardiomyopathy is found rarely. The mildest form is the adult variant, with exercise or fasting-induced rhabdomyolysis, resembling the muscle form of carnitine palmitoyl transferase 2 (CPT2) deficiency. Sudden deaths may occur as a result of cardiac conduction abnormalities in any of the three types.

Genetics

VLCADD is inherited in an autosomal recessive pattern. Gene testing should be performed if an individual is symptomatic or if a newborn screen is positive. VLCADD results from mutations in the ACADVL gene which codes for very long chain acyl-CoA dehydrogenase, the first enzyme in the breakdown of long chain (14-20 carbons) fatty acids. Some mutations lead to a complete lack of activity of this enzyme, and these are associated with the infant form. Other mutations allow for residual enzyme activity, associated with child or "adult" forms. [Andresen: 1999] Prenatal DNA testing in cells obtained by amniocentesis or chorionic villous sampling (CVS) is available.

Prognosis

Except for infantile forms that are usually lethal, prognosis is excellent if the disease is identified before the first decompensation occurs.

Prevalence

about 1/30,000 live births (VLCADD (GeneReviews))

VLCADD Module Authors

Author: Nicola Longo, MD, PhD - 11/2010
Compiled and edited by: Lynne M Kerr, MD, PhD - 11/2010
Content Last Updated: 1/2011

The authors listed above are responsible for the overall VLCADD Module. Authors contributing to individual pages in the module are listed on those pages.

Page Bibliography

Andresen BS, Olpin S, Poorthuis BJ, Scholte HR, Vianey-Saban C, Wanders R, Ijlst L, Morris A, Pourfarzam M, Bartlett K, Baumgartner ER, deKlerk JB, Schroeder LD, Corydon TJ, Lund H, Winter V, Bross P, Bolund L, Gregersen N.
Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.
Am J Hum Genet. 1999;64(2):479-94. PubMed abstract / Full Text