Abstract
Tandem mass spectrometry was adopted for newborn screening by North Carolina in April 1999. Since then, three infants with short-chain acyl-CoA dehydrogenase (SCAD) and one with isobutyryl-CoA dehydrogenase deficiency were detected on the basis of elevated butyrylcarnitine/isobutyrylcarnitine (C4-carnitine) concentrations in newborn blood spots analyzed by tandem mass spectrometry. For three SCAD-deficient infants, biochemical evaluation included a plasma acylcarnitine profile with markedly elevated C4-carnitine, urine organic acid analysis with markedly elevated ethylmalonic and 2-methylsuccinic acids, and markedly elevated [U-13C]butyrylcarnitine concentrations in medium from fibroblasts incubated with [U-13C]palmitic acid and excess l-carnitine, consistent with classic SCAD deficiency. Two of three infants diagnosed with classic SCAD deficiency remained asymptomatic; however, the third infant presented with seizures and a cerebral infarct at 10 wk of age. All three infants had putatively inactivating mutations in both alleles of the SCAD gene. The highly elevated plasma C4-carnitine levels in the three infants detected by newborn screening tandem mass spectrometry differentiated them from infants and children who were homozygous or compound heterozygous for one of two SCAD gene susceptibility variations; for the latter group the C4-carnitine levels were normal. Isobutyryl-CoA dehydrogenase deficiency in a fourth infant was confirmed after isolated elevation of C4-carnitine in the acylcarnitine profile.
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Abbreviations
- EMA:
-
ethylmalonic acid
- IBCD:
-
isobutyryl-CoA dehydrogenase
- MCAD:
-
medium chain acyl-CoA dehydrogenase
- MS/MS:
-
tandem mass spectrometry
- SCAD:
-
short chain acyl-CoA dehydrogenase
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Acknowledgements
The authors thank Dr. Diane Frazier and Dr. Joe Muenzer of the University of North Carolina for their assistance in the follow-up and evaluation of patients with abnormal MS/MS newborn screening in North Carolina. We also thank Steven Hillman and Steven Worthy for their technical assistance.
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Financial support was provided by National Institutes of Health grant R03 HD42940 (D.K.B.), National Institutes of Health grant K23 RR16060 (P.S.K.), and Genzyme Corporation (S.P.Y.). Financial support for the molecular studies at Research Unit for Molecular Medicine was provided by The Danish Medical Research Council.
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Koeberl, D., Young, S., Gregersen, N. et al. Rare Disorders of Metabolism with Elevated Butyryl- and Isobutyryl-Carnitine Detected by Tandem Mass Spectrometry Newborn Screening. Pediatr Res 54, 219–223 (2003). https://doi.org/10.1203/01.PDR.0000074972.36356.89
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DOI: https://doi.org/10.1203/01.PDR.0000074972.36356.89
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