Details

Autor(en) / Beteiligte

• Merritt, J. Lawrence
• Vedal, Sverre
• Abdenur, Jose E.
• Au, Sylvia M.
• Barshop, Bruce A.
• Feuchtbaum, Lisa
• Harding, Cary O.
• Hermerath, Cheryl
• Lorey, Fred
• Sesser, David E.
• Thompson, John D.
• Yu, Arthur

Titel

Infants suspected to have very-long chain acyl-CoA dehydrogenase deficiency from newborn screening

Ist Teil von

• Molecular genetics and metabolism, 2014-04, Vol.111 (4), p.484-492

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a fatty acid oxidation disorder with widely varying presentations that has presented a significant challenge to newborn screening (NBS). The Western States Regional Genetics Services Collaborative developed a workgroup to study infants with NBS positive for VLCADD. We performed retrospective analysis of newborns with elevated C14:1-acylcarnitine on NBS in California, Oregon, Washington, and Hawai'i including available confirmatory testing and clinical information. Overall, from 2,802,504 children screened, there were 242 cases screen-positive for VLCADD. There were 34 symptomatic true positive cases, 18 asymptomatic true positives, 112 false positives, 55 heterozygotes, 11 lost to follow-up, and 12 other disorders. One in 11,581 newborns had an abnormal NBS for suspected VLCADD. Comparison of analytes and analyte ratios from the NBS demonstrated statistically significant differences between true positive and false positive groups for C14:1, C14, C14:1/C2, and C14:1/C16. The positive predictive value for all true positive cases was 94%, 54%, and 23% when C14:1 was ≥2.0μM, ≥1.0μM, and ≥0.7μM, respectively. Sequential post-analytical analysis could reduce the referral rate in 25.8% of cases. This study is the largest reported follow-up of infants with NBS screen-positive results for suspected VLCADD and demonstrates the necessity of developing comprehensive and consistent long-term follow-up NBS systems. Application of clinical information revealed differences between symptomatic and asymptomatic children with VLCADD. Comparison of NBS analytes and analyte ratios may be valuable in developing more effective diagnostic algorithms. •We report the largest NBS follow-up study of newborns suspected to have VLCADD.•One in 11,581 newborns had an abnormal NBS for suspected VLCADD.•Retrospective application of clinical information may improve NBS algorithms.•Post-analytical analysis could reduce follow-up testing in 25.8% of cases.•There is a critical need for harmonization of clinical follow-up practices.