Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening.
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.
Koeberl
Dwight D
DD
Division of Medical Genetics, DUMC 3528, Bell Building Room 237, Trent Duke University Medical Center, Durham, NC 27710, U.S.A. koebe001@mc.duke.edu
Young
Sarah P
SP
Gregersen
Niels S
NS
Vockley
Jerry
J
Smith
Wendy E
WE
Benjamin
Daniel Kelly
DK
An
Yan
Y
Weavil
Susan D
SD
Chaing
Shu H
SH
Bali
Deeksha
D
McDonald
Marie T
MT
Kishnani
Priya S
PS
Chen
Y-T
YT
Millington
David S
DS
D044926:Butyryl-CoA Dehydrogenase / Q000172:deficiency; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D013058:Mass Spectrometry; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000378:metabolism; D015997:Neonatal Screening / Q000379:methods*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency
C020381:isobutyryl-1-carnitine; C427065:butyrylcarnitine; D044925:Oxidoreductases Acting on CH-CH Group Donors; D044926:Butyryl-CoA Dehydrogenase; C038808:2-methylacyl-CoA dehydrogenase; D002331:Carnitine