title: Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database.
abstract: 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.
authors.affiliation: Duke University, USA. Electronic address: loren.pena@duke.edu.
authors.forename: Loren D M
authors.initials: LD
authors.lastname: Pena
authors.affiliation: Oregon Health and Science University, USA.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: van Calcar
authors.affiliation: Oregon Health and Science University, USA.
authors.forename: Joyanna
authors.initials: J
authors.lastname: Hansen
authors.affiliation: Michigan Public Health Institute, USA.
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Edick
authors.affiliation: University of Pittsburgh School of Medicine, USA.
authors.forename: Cate
authors.initials: C
authors.lastname: Walsh Vockley
authors.affiliation: Cincinnati Children's Hospital Medical Center, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Leslie
authors.affiliation: Michigan Public Health Institute, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cameron
authors.affiliation: University of Pittsburgh School of Medicine, USA.
authors.forename: Al-Walid
authors.initials: AW
authors.lastname: Mohsen
authors.affiliation: University of Minnesota, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Berry
authors.affiliation: Genetic Metabolic Center for Education, USA.
authors.forename: Georgianne L
authors.initials: GL
authors.lastname: Arnold
authors.affiliation: University of Pittsburgh School of Medicine, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Vockley
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D000293:Adolescent; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D002648:Child; D002675:Child, Preschool; D000080984:Congenital Bone Marrow Failure Syndromes; D003402:Creatine Kinase / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D028361:Mitochondrial Diseases / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D009135:Muscular Diseases / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D015997:Neonatal Screening; D012189:Retrospective Studies
chemical_list: C116917:acylcarnitine; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D003402:Creatine Kinase; D002331:Carnitine
keywords: Fatty acid oxidation disorder; Inborn errors of metabolism; Natural history; Newborn screening; Rhabdomyolysis; Very long chain acyl-CoA dehydrogenase deficiency