221 newborn-screened neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency: Findings from the Inborn Errors of Metabolism Collaborative

Kristi Bentler, Shaohui Zhai, Sara A. Elsbecker, Georgianne L. Arnold, Barbara K. Burton, Jerry Vockley, Cynthia A. Cameron, Sally J. Hiner, Mathew J. Edick, Susan A. Berry, Janet Thomas, Melinda Dodge, Rani Singh, Sangeetha Lakshman, Katie Coakley, Adrya Stembridge, Alvaro Serrano Russi, Emily Phillips, Barbara Burton, Clare Edano & 62 others Sheela Shrestha, George Hoganson, Lauren Dwyer, Bryan Hainline, Susan Romie, Sarah Hainline, Alexander Asamoah, Kara Goodin, Cecilia Rajakaruna, Kelly Jackson, Ada Hamosh, Hilary Vernon, Nancy Smith, Ayesha Ahmad, Sue Lipinski, Gerald Feldman, Susan Berry, Sara Elsbecker, Kristi Bentler, Esperanza Font-Montgomery, Dawn Peck, Loren D M Pena, Dwight D. Koeberl, Yong hui Jiang, Priya S. Kishnani, William Rizzo, Machelle Dawson, Nancy Ambrose, Paul Levy, David Kronn, Chin to Fong, Kristin D'Aco, Theresa Hart, Richard Erbe, Melissa Samons, Nancy Leslie, Racheal Powers, Dennis Bartholomew, Melanie Goff, Sandy vanCalcar, Joyanna Hansen, Georgianne Arnold, Jerry Vockley, Cate Walsh-Vockley, William Rhead, David Dimmock, Paula Engelking, Cassie Bird, Ashley Swan, Jessica Scott Schwoerer, Sonja Henry, Tara Chandra Narumanchi, Marybeth Hummel, Jennie Wilkins, Laura Davis-Keppen, Quinn Stein, Rebecca Loman, Cynthia Cameron, Mathew J. Edick, Sally J. Hiner, Kaitlin Justice, Shaohui Zhai

Research output: Contribution to journalArticle

Abstract

Introduction There is limited understanding of relationships between genotype, phenotype and other conditions contributing to health in neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) identified through newborn screening. Methods Retrospective analysis of comprehensive data from a cohort of 221 newborn-screened subjects identified as affected with MCADD in the Inborn Errors of Metabolism – Information System (IBEM-IS), a long term follow-up database of the Inborn Errors of Metabolism Collaborative, was performed. Results The average age at notification of first newborn screen results to primary care or metabolic providers was 7.45 days. The average octanoylcarnitine (C8) value on first newborn screen was 11.2 μmol/L (median 8.6, range 0.36–43.91). A higher C8 level correlated with an earlier first subspecialty visit. Subjects with low birth weight had significantly lower C8 values. Significantly higher C8 values were found in symptomatic newborns, in newborns with abnormal lab testing in addition to newborn screening and/or diagnostic tests, and in subjects homozygous for the c.985A > G ACADM gene mutation or compound heterozygous for the c.985A > G mutation and deletions or other known highly deleterious mutations. Subjects with neonatal symptoms, or neonatal abnormal labs, or neonatal triggers were more likely to have at least one copy of the severe c.985A > G ACADM gene mutation. C8 and genotype category were significant predictors of the likelihood of having neonatal symptoms. Neonates with select triggers were more likely to have symptoms and laboratory abnormalities. Conclusions This collaborative study is the first in the United States to describe health associations of a large cohort of newborn-screened neonates identified as affected with MCADD. The IBEM-IS has utility as a platform to better understand the characteristics of individuals with newborn-screened conditions and their follow-up interactions with the health system.

Original languageEnglish (US)
Pages (from-to)75-82
Number of pages8
JournalMolecular Genetics and Metabolism
Volume119
Issue number1-2
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Fingerprint

Acyl-CoA Dehydrogenase
Inborn Errors Metabolism
Newborn Infant
Metabolism
Jejunoileal Bypass
Cyclic AMP Receptor Protein
Dental Materials
Extracorporeal Circulation
Mutation
Health
Hexosaminidase A
Blood Stains
Acromion
Information Systems
Genotype
Genes
Sequence Deletion
Low Birth Weight Infant
Routine Diagnostic Tests
Primary Health Care

Keywords

  • ACADM
  • Inborn error of metabolism
  • MCAD
  • Medium-chain acyl-coenzyme A dehydrogenase deficiency
  • Newborn screening
  • Octanoylcarnitine

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

221 newborn-screened neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency : Findings from the Inborn Errors of Metabolism Collaborative. / Bentler, Kristi; Zhai, Shaohui; Elsbecker, Sara A.; Arnold, Georgianne L.; Burton, Barbara K.; Vockley, Jerry; Cameron, Cynthia A.; Hiner, Sally J.; Edick, Mathew J.; Berry, Susan A.; Thomas, Janet; Dodge, Melinda; Singh, Rani; Lakshman, Sangeetha; Coakley, Katie; Stembridge, Adrya; Russi, Alvaro Serrano; Phillips, Emily; Burton, Barbara; Edano, Clare; Shrestha, Sheela; Hoganson, George; Dwyer, Lauren; Hainline, Bryan; Romie, Susan; Hainline, Sarah; Asamoah, Alexander; Goodin, Kara; Rajakaruna, Cecilia; Jackson, Kelly; Hamosh, Ada; Vernon, Hilary; Smith, Nancy; Ahmad, Ayesha; Lipinski, Sue; Feldman, Gerald; Berry, Susan; Elsbecker, Sara; Bentler, Kristi; Font-Montgomery, Esperanza; Peck, Dawn; Pena, Loren D M; Koeberl, Dwight D.; Jiang, Yong hui; Kishnani, Priya S.; Rizzo, William; Dawson, Machelle; Ambrose, Nancy; Levy, Paul; Kronn, David; Fong, Chin to; D'Aco, Kristin; Hart, Theresa; Erbe, Richard; Samons, Melissa; Leslie, Nancy; Powers, Racheal; Bartholomew, Dennis; Goff, Melanie; vanCalcar, Sandy; Hansen, Joyanna; Arnold, Georgianne; Vockley, Jerry; Walsh-Vockley, Cate; Rhead, William; Dimmock, David; Engelking, Paula; Bird, Cassie; Swan, Ashley; Schwoerer, Jessica Scott; Henry, Sonja; Narumanchi, Tara Chandra; Hummel, Marybeth; Wilkins, Jennie; Davis-Keppen, Laura; Stein, Quinn; Loman, Rebecca; Cameron, Cynthia; Edick, Mathew J.; Hiner, Sally J.; Justice, Kaitlin; Zhai, Shaohui.

In: Molecular Genetics and Metabolism, Vol. 119, No. 1-2, 01.09.2016, p. 75-82.

Research output: Contribution to journalArticle

Bentler, K, Zhai, S, Elsbecker, SA, Arnold, GL, Burton, BK, Vockley, J, Cameron, CA, Hiner, SJ, Edick, MJ, Berry, SA, Thomas, J, Dodge, M, Singh, R, Lakshman, S, Coakley, K, Stembridge, A, Russi, AS, Phillips, E, Burton, B, Edano, C, Shrestha, S, Hoganson, G, Dwyer, L, Hainline, B, Romie, S, Hainline, S, Asamoah, A, Goodin, K, Rajakaruna, C, Jackson, K, Hamosh, A, Vernon, H, Smith, N, Ahmad, A, Lipinski, S, Feldman, G, Berry, S, Elsbecker, S, Bentler, K, Font-Montgomery, E, Peck, D, Pena, LDM, Koeberl, DD, Jiang, YH, Kishnani, PS, Rizzo, W, Dawson, M, Ambrose, N, Levy, P, Kronn, D, Fong, CT, D'Aco, K, Hart, T, Erbe, R, Samons, M, Leslie, N, Powers, R, Bartholomew, D, Goff, M, vanCalcar, S, Hansen, J, Arnold, G, Vockley, J, Walsh-Vockley, C, Rhead, W, Dimmock, D, Engelking, P, Bird, C, Swan, A, Schwoerer, JS, Henry, S, Narumanchi, TC, Hummel, M, Wilkins, J, Davis-Keppen, L, Stein, Q, Loman, R, Cameron, C, Edick, MJ, Hiner, SJ, Justice, K & Zhai, S 2016, '221 newborn-screened neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency: Findings from the Inborn Errors of Metabolism Collaborative' Molecular Genetics and Metabolism, vol 119, no. 1-2, pp. 75-82. DOI: 10.1016/j.ymgme.2016.07.002

Bentler, Kristi; Zhai, Shaohui; Elsbecker, Sara A.; Arnold, Georgianne L.; Burton, Barbara K.; Vockley, Jerry; Cameron, Cynthia A.; Hiner, Sally J.; Edick, Mathew J.; Berry, Susan A.; Thomas, Janet; Dodge, Melinda; Singh, Rani; Lakshman, Sangeetha; Coakley, Katie; Stembridge, Adrya; Russi, Alvaro Serrano; Phillips, Emily; Burton, Barbara; Edano, Clare; Shrestha, Sheela; Hoganson, George; Dwyer, Lauren; Hainline, Bryan; Romie, Susan; Hainline, Sarah; Asamoah, Alexander; Goodin, Kara; Rajakaruna, Cecilia; Jackson, Kelly; Hamosh, Ada; Vernon, Hilary; Smith, Nancy; Ahmad, Ayesha; Lipinski, Sue; Feldman, Gerald; Berry, Susan; Elsbecker, Sara; Bentler, Kristi; Font-Montgomery, Esperanza; Peck, Dawn; Pena, Loren D M; Koeberl, Dwight D.; Jiang, Yong hui; Kishnani, Priya S.; Rizzo, William; Dawson, Machelle; Ambrose, Nancy; Levy, Paul; Kronn, David; Fong, Chin to; D'Aco, Kristin; Hart, Theresa; Erbe, Richard; Samons, Melissa; Leslie, Nancy; Powers, Racheal; Bartholomew, Dennis; Goff, Melanie; vanCalcar, Sandy; Hansen, Joyanna; Arnold, Georgianne; Vockley, Jerry; Walsh-Vockley, Cate; Rhead, William; Dimmock, David; Engelking, Paula; Bird, Cassie; Swan, Ashley; Schwoerer, Jessica Scott; Henry, Sonja; Narumanchi, Tara Chandra; Hummel, Marybeth; Wilkins, Jennie; Davis-Keppen, Laura; Stein, Quinn; Loman, Rebecca; Cameron, Cynthia; Edick, Mathew J.; Hiner, Sally J.; Justice, Kaitlin; Zhai, Shaohui / 221 newborn-screened neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency : Findings from the Inborn Errors of Metabolism Collaborative.

In: Molecular Genetics and Metabolism, Vol. 119, No. 1-2, 01.09.2016, p. 75-82.

Research output: Contribution to journalArticle

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title = "221 newborn-screened neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency: Findings from the Inborn Errors of Metabolism Collaborative",
abstract = "Introduction There is limited understanding of relationships between genotype, phenotype and other conditions contributing to health in neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) identified through newborn screening. Methods Retrospective analysis of comprehensive data from a cohort of 221 newborn-screened subjects identified as affected with MCADD in the Inborn Errors of Metabolism – Information System (IBEM-IS), a long term follow-up database of the Inborn Errors of Metabolism Collaborative, was performed. Results The average age at notification of first newborn screen results to primary care or metabolic providers was 7.45 days. The average octanoylcarnitine (C8) value on first newborn screen was 11.2 μmol/L (median 8.6, range 0.36–43.91). A higher C8 level correlated with an earlier first subspecialty visit. Subjects with low birth weight had significantly lower C8 values. Significantly higher C8 values were found in symptomatic newborns, in newborns with abnormal lab testing in addition to newborn screening and/or diagnostic tests, and in subjects homozygous for the c.985A > G ACADM gene mutation or compound heterozygous for the c.985A > G mutation and deletions or other known highly deleterious mutations. Subjects with neonatal symptoms, or neonatal abnormal labs, or neonatal triggers were more likely to have at least one copy of the severe c.985A > G ACADM gene mutation. C8 and genotype category were significant predictors of the likelihood of having neonatal symptoms. Neonates with select triggers were more likely to have symptoms and laboratory abnormalities. Conclusions This collaborative study is the first in the United States to describe health associations of a large cohort of newborn-screened neonates identified as affected with MCADD. The IBEM-IS has utility as a platform to better understand the characteristics of individuals with newborn-screened conditions and their follow-up interactions with the health system.",
keywords = "ACADM, Inborn error of metabolism, MCAD, Medium-chain acyl-coenzyme A dehydrogenase deficiency, Newborn screening, Octanoylcarnitine",
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T1 - 221 newborn-screened neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency

T2 - Molecular Genetics and Metabolism

AU - Bentler,Kristi

AU - Zhai,Shaohui

AU - Elsbecker,Sara A.

AU - Arnold,Georgianne L.

AU - Burton,Barbara K.

AU - Vockley,Jerry

AU - Cameron,Cynthia A.

AU - Hiner,Sally J.

AU - Edick,Mathew J.

AU - Berry,Susan A.

AU - Thomas,Janet

AU - Dodge,Melinda

AU - Singh,Rani

AU - Lakshman,Sangeetha

AU - Coakley,Katie

AU - Stembridge,Adrya

AU - Russi,Alvaro Serrano

AU - Phillips,Emily

AU - Burton,Barbara

AU - Edano,Clare

AU - Shrestha,Sheela

AU - Hoganson,George

AU - Dwyer,Lauren

AU - Hainline,Bryan

AU - Romie,Susan

AU - Hainline,Sarah

AU - Asamoah,Alexander

AU - Goodin,Kara

AU - Rajakaruna,Cecilia

AU - Jackson,Kelly

AU - Hamosh,Ada

AU - Vernon,Hilary

AU - Smith,Nancy

AU - Ahmad,Ayesha

AU - Lipinski,Sue

AU - Feldman,Gerald

AU - Berry,Susan

AU - Elsbecker,Sara

AU - Bentler,Kristi

AU - Font-Montgomery,Esperanza

AU - Peck,Dawn

AU - Pena,Loren D M

AU - Koeberl,Dwight D.

AU - Jiang,Yong hui

AU - Kishnani,Priya S.

AU - Rizzo,William

AU - Dawson,Machelle

AU - Ambrose,Nancy

AU - Levy,Paul

AU - Kronn,David

AU - Fong,Chin to

AU - D'Aco,Kristin

AU - Hart,Theresa

AU - Erbe,Richard

AU - Samons,Melissa

AU - Leslie,Nancy

AU - Powers,Racheal

AU - Bartholomew,Dennis

AU - Goff,Melanie

AU - vanCalcar,Sandy

AU - Hansen,Joyanna

AU - Arnold,Georgianne

AU - Vockley,Jerry

AU - Walsh-Vockley,Cate

AU - Rhead,William

AU - Dimmock,David

AU - Engelking,Paula

AU - Bird,Cassie

AU - Swan,Ashley

AU - Schwoerer,Jessica Scott

AU - Henry,Sonja

AU - Narumanchi,Tara Chandra

AU - Hummel,Marybeth

AU - Wilkins,Jennie

AU - Davis-Keppen,Laura

AU - Stein,Quinn

AU - Loman,Rebecca

AU - Cameron,Cynthia

AU - Edick,Mathew J.

AU - Hiner,Sally J.

AU - Justice,Kaitlin

AU - Zhai,Shaohui

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Introduction There is limited understanding of relationships between genotype, phenotype and other conditions contributing to health in neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) identified through newborn screening. Methods Retrospective analysis of comprehensive data from a cohort of 221 newborn-screened subjects identified as affected with MCADD in the Inborn Errors of Metabolism – Information System (IBEM-IS), a long term follow-up database of the Inborn Errors of Metabolism Collaborative, was performed. Results The average age at notification of first newborn screen results to primary care or metabolic providers was 7.45 days. The average octanoylcarnitine (C8) value on first newborn screen was 11.2 μmol/L (median 8.6, range 0.36–43.91). A higher C8 level correlated with an earlier first subspecialty visit. Subjects with low birth weight had significantly lower C8 values. Significantly higher C8 values were found in symptomatic newborns, in newborns with abnormal lab testing in addition to newborn screening and/or diagnostic tests, and in subjects homozygous for the c.985A > G ACADM gene mutation or compound heterozygous for the c.985A > G mutation and deletions or other known highly deleterious mutations. Subjects with neonatal symptoms, or neonatal abnormal labs, or neonatal triggers were more likely to have at least one copy of the severe c.985A > G ACADM gene mutation. C8 and genotype category were significant predictors of the likelihood of having neonatal symptoms. Neonates with select triggers were more likely to have symptoms and laboratory abnormalities. Conclusions This collaborative study is the first in the United States to describe health associations of a large cohort of newborn-screened neonates identified as affected with MCADD. The IBEM-IS has utility as a platform to better understand the characteristics of individuals with newborn-screened conditions and their follow-up interactions with the health system.

AB - Introduction There is limited understanding of relationships between genotype, phenotype and other conditions contributing to health in neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) identified through newborn screening. Methods Retrospective analysis of comprehensive data from a cohort of 221 newborn-screened subjects identified as affected with MCADD in the Inborn Errors of Metabolism – Information System (IBEM-IS), a long term follow-up database of the Inborn Errors of Metabolism Collaborative, was performed. Results The average age at notification of first newborn screen results to primary care or metabolic providers was 7.45 days. The average octanoylcarnitine (C8) value on first newborn screen was 11.2 μmol/L (median 8.6, range 0.36–43.91). A higher C8 level correlated with an earlier first subspecialty visit. Subjects with low birth weight had significantly lower C8 values. Significantly higher C8 values were found in symptomatic newborns, in newborns with abnormal lab testing in addition to newborn screening and/or diagnostic tests, and in subjects homozygous for the c.985A > G ACADM gene mutation or compound heterozygous for the c.985A > G mutation and deletions or other known highly deleterious mutations. Subjects with neonatal symptoms, or neonatal abnormal labs, or neonatal triggers were more likely to have at least one copy of the severe c.985A > G ACADM gene mutation. C8 and genotype category were significant predictors of the likelihood of having neonatal symptoms. Neonates with select triggers were more likely to have symptoms and laboratory abnormalities. Conclusions This collaborative study is the first in the United States to describe health associations of a large cohort of newborn-screened neonates identified as affected with MCADD. The IBEM-IS has utility as a platform to better understand the characteristics of individuals with newborn-screened conditions and their follow-up interactions with the health system.

KW - ACADM

KW - Inborn error of metabolism

KW - MCAD

KW - Medium-chain acyl-coenzyme A dehydrogenase deficiency

KW - Newborn screening

KW - Octanoylcarnitine

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