Spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by newborn screening
Department of Pediatrics; New England Newborn Screening Program
Acyl-CoA Dehydrogenase; Biological Markers; Breast Feeding; Carnitine; Humans; Infant Formula; Infant, Newborn; *Neonatal Screening; Point Mutation; Sequence Analysis, DNA
Genetics and Genomics | Life Sciences | Medical Genetics | Medicine and Health Sciences | Pediatrics
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.
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Citation: Pediatrics. 2008 May;121(5):e1108-14. Link to article on publisher's site