MS/MS-based newborn and family screening detects asymptomatic patients with very-long-chain acyl-CoA dehydrogenase deficiency.
OBJECTIVE
To determine whether asymptomatic persons with biochemical evidence of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency identified through expanded newborn screening with tandem mass spectometry have confirmed disease.


METHODS
We characterized 8 asymptomatic VLCAD-deficient individuals by enzyme and/or mutational analysis and compared them with clinically diagnosed, symptomatic patients with regard to mutations, enzyme activity, phenotype, and age of disease onset.


RESULTS
VLCAD molecular analyses in 6 unrelated patients revealed the previously reported V243A mutation, associated with hepatic or myopathic phenotypes, on 7/12 alleles. All other mutations were also missense mutations. Residual VLCAD activities of 6% to 11% of normal were consistent with milder phenotypes. In these identified individuals treated prospectively with dietary modification as preventive measures, clinical symptoms did not develop during follow-up.


CONCLUSIONS
MS/MS-based newborn screening correctly identifies VLCAD-deficient individuals. Based on mutational and enzymatic findings, these infants probably are at risk of future disease. Because life-threatening metabolic derangement can occur even in otherwise mild phenotypes, we advocate universal newborn screening programs for VLCAD deficiency to detect affected patients and prevent development of metabolic crises. Longer-term follow-up is essential to define outcomes, the definite risk of future disease, and appropriate treatment recommendations.
D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000097:blood* / Q000172:deficiency* / Q000235:genetics; D017668:Age of Onset; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003677:Deficiency Diseases / Q000097:blood* / Q000201:enzymology / Q000235:genetics*; D005190:Family; D044943:Fatty Acid Desaturases / Q000097:blood* / Q000172:deficiency* / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D013058:Mass Spectrometry; D015997:Neonatal Screening; D010641:Phenotype; D015203:Reproducibility of Results
D044943:Fatty Acid Desaturases; D044942:Acyl-CoA Dehydrogenase, Long-Chain