Outcomes and Genotype-Phenotype Correlations in 52 Individuals With VLCAD Deficiency Diagnosed by NBS and Enrolled in the IBEM-IS Database

Mol Genet Metab. 2016 Aug;118(4):272-81. doi: 10.1016/j.ymgme.2016.05.007. Epub 2016 May 13.


Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency can present at various ages from the neonatal period to adulthood, and poses the greatest risk of complications during intercurrent illness or after prolonged fasting. Early diagnosis, treatment, and surveillance can reduce mortality; hence, the disorder is included in the newborn Recommended Uniform Screening Panel (RUSP) in the United States. The Inborn Errors of Metabolism Information System (IBEM-IS) was established in 2007 to collect longitudinal information on individuals with inborn errors of metabolism included in newborn screening (NBS) programs, including VLCAD deficiency. We retrospectively analyzed early outcomes for individuals who were diagnosed with VLCAD deficiency by NBS and describe initial presentations, diagnosis, clinical outcomes and treatment in a cohort of 52 individuals ages 1-18years. Maternal prenatal symptoms were not reported, and most newborns remained asymptomatic. Cardiomyopathy was uncommon in the cohort, diagnosed in 2/52 cases. Elevations in creatine kinase were a common finding, and usually first occurred during the toddler period (1-3years of age). Diagnostic evaluations required several testing modalities, most commonly plasma acylcarnitine profiles and molecular testing. Functional testing, including fibroblast acylcarnitine profiling and white blood cell or fibroblast enzyme assay, is a useful diagnostic adjunct if uncharacterized mutations are identified.

Keywords: Fatty acid oxidation disorder; Inborn errors of metabolism; Natural history; Newborn screening; Rhabdomyolysis; Very long chain acyl-CoA dehydrogenase deficiency.

MeSH terms

  • Acyl-CoA Dehydrogenase, Long-Chain / blood
  • Acyl-CoA Dehydrogenase, Long-Chain / deficiency*
  • Acyl-CoA Dehydrogenase, Long-Chain / genetics*
  • Adolescent
  • Carnitine / analogs & derivatives
  • Carnitine / blood
  • Child
  • Child, Preschool
  • Congenital Bone Marrow Failure Syndromes
  • Creatine Kinase / genetics
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Lipid Metabolism, Inborn Errors / blood
  • Lipid Metabolism, Inborn Errors / genetics*
  • Lipid Metabolism, Inborn Errors / physiopathology
  • Male
  • Mitochondrial Diseases / blood
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / physiopathology
  • Muscular Diseases / blood
  • Muscular Diseases / genetics*
  • Muscular Diseases / physiopathology
  • Mutation
  • Neonatal Screening*
  • Retrospective Studies


  • acylcarnitine
  • Acyl-CoA Dehydrogenase, Long-Chain
  • Creatine Kinase
  • Carnitine

Supplementary concepts

  • VLCAD deficiency