Spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by newborn screening.

Abstract

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 microM) 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 microM) 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.

• Authors: Ho-Wen Hsu, Thomas H Zytkovicz, Anne Marie Comeau, Arnold W Strauss, Deborah Marsden, Vivian E Shih, George F Grady, Roger B Eaton
• Journal: Pediatrics (Pediatrics) Vol. 121 Issue 5 Pg. e1108-14 (May 2008) ISSN: 1098-4275 [Electronic] United States
• PMID: 18450854 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biomarkers
• decanoylcarnitine
• Acyl-CoA Dehydrogenase
• octanoylcarnitine
• Carnitine

Topics

• Acyl-CoA Dehydrogenase (deficiency, genetics)
• Biomarkers (blood)
• Breast Feeding
• Carnitine (analogs & derivatives, blood)
• Humans
• Infant Formula
• Infant, Newborn
• Neonatal Screening
• Point Mutation
• Sequence Analysis, DNA