Tandem mass spectrometry screening for very long-chain acyl-CoA dehydrogenase deficiency: the value of second-tier enzyme testing.
OBJECTIVE
To evaluate newborn screening (NBS) for very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), we further characterized newborns with elevation of one or all C14-carnitine derivatives on NBS from a total of 90 338 newborns.


METHODS
Palmitoyl-CoA oxidation was performed in lymphocytes to define very long-chain acyl-CoA dehydrogenase function. Molecular analysis followed in children with residual activities<50%. The acylcarnitine pattern on days 2 to 3 of life was evaluated thoroughly to define possible discrimination markers.


RESULTS
Forty newborns with increased C14:1-carnitine were identified (1:2500). In 2 newborns, VLCADD was confirmed with enzyme and molecular analyses (prevalence, 1:50,000). One of these newborns had normal results on a second screening. Also, the combination of absolute acylcarnitine values and acylcarnitine ratios did not allow correct identification of the newborn as a patient with VLCADD.


CONCLUSIONS
Reliable diagnosis is not feasible with acylcarnitine analysis alone. Enzyme analysis in lymphocytes is a reliable and rapid method for correctly assessing all newborns with VLCADD and should be carried out in all newborns identified during the first screening, regardless of the results of a later acylcarnitine profile.
Spiekerkoetter
Ute
U
Department of General Pediatrics, University Children's Hospital, Duesseldorf, Germany.
Haussmann
Ulrike
U
Mueller
Martina
M
ter Veld
Frank
F
Stehn
Maren
M
Santer
Rene
R
Lukacs
Zoltan
Z
D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency*; D002331:Carnitine / Q000031:analogs & derivatives / Q000032:analysis; D004796:Clinical Enzyme Tests / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D008661:Metabolism, Inborn Errors / Q000175:diagnosis*; D015997:Neonatal Screening; D053719:Tandem Mass Spectrometry / Q000295:instrumentation*
C116917:acylcarnitine; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002331:Carnitine