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


CONCLUSIONS
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.
Hsu
Ho-Wen
HW
New England Newborn Screening Program, University of Massachusetts Medical School, 305 South St, Jamaica Plain, MA 02130, USA. ho-wen.hsu@umassmed.edu
Zytkovicz
Thomas H
TH
Comeau
Anne Marie
AM
Strauss
Arnold W
AW
Marsden
Deborah
D
Shih
Vivian E
VE
Grady
George F
GF
Eaton
Roger B
RB
D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D001942:Breast Feeding; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D041943:Infant Formula; D007231:Infant, Newborn; D015997:Neonatal Screening; D017354:Point Mutation; D017422:Sequence Analysis, DNA
D015415:Biomarkers; C002893:decanoylcarnitine; D042964:Acyl-CoA Dehydrogenase; C008698:octanoylcarnitine; D002331:Carnitine