Published online May 1, 2008
PEDIATRICS Vol. 121 No. 5 May 2008, pp. e1108-e1114 (doi:10.1542/peds.2007-1993)
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Hsu, H.-W.
Right arrow Articles by Eaton, R. B.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hsu, H.-W.
Right arrow Articles by Eaton, R. B.
Related Collections
Right arrow Premature & Newborn

ARTICLE

Spectrum of Medium-Chain Acyl-CoA Dehydrogenase Deficiency Detected by Newborn Screening

Ho-Wen Hsu, MDa, Thomas H. Zytkovicz, PhDa, Anne Marie Comeau, PhDa, Arnold W. Strauss, MDb, Deborah Marsden, MDc, Vivian E. Shih, MDd, George F. Grady, MDa and Roger B. Eaton, PhDa

a Department of Pediatrics, New England Newborn Screening Program, University of Massachusetts Medical School, Jamaica Plain, Massachusetts
b Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
c Department of Pediatrics, Children's Hospital Boston, Boston, Massachusetts
d Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts

OBJECTIVE. Our goal was to describe the clinical spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by routine newborn screening and assess factors associated with elevations of octanoylcarnitine in newborns and characteristics associated with adverse clinical consequences of medium-chain acyl-CoA dehydrogenase deficiency.

METHODS. The first 47 medium-chain acyl-CoA dehydrogenase deficiency cases detected by the New England Newborn Screening Program were classified according to initial and follow-up octanoylcarnitine values, octanoylcarnitine-decanoylcarnitine ratios, medium-chain acyl-CoA dehydrogenase genotype, follow-up biochemical parameters, and feeding by breast milk or formula.

RESULTS. All 20 patients who were homozygous for 985A->G had high initial octanoylcarnitine values (7.0–36.8 µM) and octanoylcarnitine-decanoylcarnitine ratios (7.0–14.5), whereas the 27 patients with 0 to 1 copy of 985A->G exhibited a wide range of octanoylcarnitine values (0.5–28.6 µM) and octanoylcarnitine-decanoylcarnitine ratios (0.8–12.7). Initial newborn octanoylcarnitine values decreased by days 5 to 8, but the octanoylcarnitine-decanoylcarnitine ratio generally remained stable. Among 985A->G homozygotes, breastfed newborns had higher initial octanoylcarnitine values than newborns who received formula. Adverse events occurred in 5 children, 4 985A->G homozygotes and 1 compound heterozygote with a very high initial octanoylcarnitine: 2 survived severe neonatal hypoglycemia, 1 survived a severe hypoglycemic episode at 15 months of age, and 2 died as a result of medium-chain acyl-CoA dehydrogenase deficiency at ages 11 and 33 months.

CONCLUSION. Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency has detected cases with a wide range of genotypes and biochemical abnormalities. Although most children do well, adverse outcomes have not been entirely avoided. Assessment of potential risk and determination of appropriate treatment remain a challenge.

Key Words: newborn screening • metabolic disorders • fatty acid oxidation defects

Abbreviations: MCAD—medium-chain acyl-CoA dehydrogenase • C8—octanoylcarnitine • PCR—polymerase chain reaction • C10—decanoylcarnitine

Accepted Oct 12, 2007.