TY - JOUR
T1 - Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database
AU - Pena, Loren D.M.
AU - van Calcar, Sandra C.
AU - Hansen, Joyanna
AU - Edick, Mathew J.
AU - Walsh Vockley, Cate
AU - Leslie, Nancy
AU - Cameron, Cynthia
AU - Mohsen, Al Walid
AU - Berry, Susan A.
AU - Arnold, Georgianne L.
AU - Vockley, Jerry
N1 - Funding Information:
This research was facilitated by the Newborn Screening Translational Research Network (“NBSTRN”), which is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (HHSN275201300011C).
Funding Information:
Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) , National Institutes of Health under award number 5R01HD069039 . JV was supported in part by R01DK78755. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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 1–18 years. 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 (1–3 years 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.
AB - 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 1–18 years. 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 (1–3 years 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.
KW - Fatty acid oxidation disorder
KW - Inborn errors of metabolism
KW - Natural history
KW - Newborn screening
KW - Rhabdomyolysis
KW - Very long chain acyl-CoA dehydrogenase deficiency
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U2 - 10.1016/j.ymgme.2016.05.007
DO - 10.1016/j.ymgme.2016.05.007
M3 - Article
C2 - 27209629
AN - SCOPUS:84969245834
VL - 118
SP - 272
EP - 281
JO - Biochemical Medicine and Metabolic Biology
JF - Biochemical Medicine and Metabolic Biology
SN - 1096-7192
IS - 4
ER -