VLCAD deficiency: pitfalls in newborn screening and confirmation of diagnosis by mutation analysis.
We diagnosed six newborn babies with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) through newborn screening in three years in Victoria (prevalence rate: 1:31,500). We identified seven known and two new mutations in our patients (2/6 homozygotes; 4/6 compound heterozygotes). Blood samples taken at age 48-72 h were diagnostic whereas repeat samples at an older age were normal in 4/6 babies. Urine analysis was normal in 5/5. We conclude that the timing of blood sampling for newborn screening is important and that it is important to perform mutation analysis to avoid false-negative diagnoses of VLCADD in asymptomatic newborn babies. In view of the emerging genotype-phenotype correlation in this disorder, the information derived from mutational analysis can be helpful in designing the appropriate follow-up and therapeutic regime for these patients.
Metabolic Service and Newborn Screening Laboratory, Genetic Health Services Victoria, Melbourne, Australia. avihu.boneh@ghsv.org.au
A
A
Boneh
B S
BS
Andresen
N
N
Gregersen
M
M
Ibrahim
N
N
Tzanakos
H
H
Peters
J
J
Yaplito-Lee
J J
JJ
Pitt
D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics; D001800:Blood Specimen Collection / Q000379:methods; D002331:Carnitine / Q000378:metabolism / Q000627:therapeutic use; D004252:DNA Mutational Analysis / Q000379:methods; D006801:Humans; D007231:Infant, Newborn; D013058:Mass Spectrometry; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D015997:Neonatal Screening / Q000295:instrumentation / Q000379:methods; D022821:RNA Splice Sites / Q000235:genetics
D022821:RNA Splice Sites; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002331:Carnitine