PMID- 30721391
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1868-310X (Print)
IS  - 1868-6001 (Electronic)
IS  - 1868-310X (Linking)
VI  - 10
IP  - 4
DP  - 2019 Oct
TI  - Misclassification of VLCAD carriers due to variable confirmatory testing after a 
      positive NBS result.
PG  - 447-451
LID - 10.1007/s12687-019-00409-8 [doi]
AB  - The Iowa Newborn Screening (NBS) Program began screening for very long-chain 
      acyl-CoA dehydrogenase deficiency (VLCAD) in 2003. Untreated VLCAD can lead to 
      liver failure, heart failure, and death. Current confirmatory testing 
      recommendations by the American College of Medical Genetics (ACMG) for VLCAD list 
      molecular and functional analysis (i.e., fibroblast fatty acid oxidation probe) 
      as optional. This can lead to misclassification of VLCAD carriers as false 
      positives. Iowa implemented a comprehensive VLCAD confirmatory testing algorithm 
      at the beginning of 2016 that included both molecular and fibroblast analysis. 
      Here, we compare the historic multi-algorithmic confirmatory testing protocol 
      (2005-2016) to this comprehensive protocol (2016-2017). A metabolic specialist 
      reviewed all medical records and NBS data for each out-of-range VLCAD that fell 
      in each testing period. During the comprehensive testing period, 48,651 specimens 
      were screened. Thirteen individuals with out-of-range C14:1 results were 
      classified as follows after review: ten carriers, zero true positives, zero false 
      positives, zero lost to follow-up, and four unable to assess carrier status. 
      During the variable testing period, a total of 486,566 specimens were screened. 
      Eighty-five individuals with out-of-range C14:1 were classified as follows: 45 
      carriers, two true positives, four false positives, four lost to follow-up, and 
      30 unable to assess carrier status. Our findings suggest that many out-of-range 
      VLCAD cases that do not receive molecular confirmatory testing could be carriers 
      mistakenly classified as false positives. We recommend comprehensive molecular 
      and functional testing for all children with out-of-range VLCAD NBS results.
FAU - Atkins, Anne E
AU  - Atkins AE
AUID- ORCID: 0000-0002-5284-6089
AD  - Center for Translational Research, Children's National Health System, Washington, 
      DC, USA. aatkins@childrensnational.org.
FAU - Tarini, Beth A
AU  - Tarini BA
AD  - Center for Translational Research, Children's National Health System, Washington, 
      DC, USA.
FAU - Phillips, Emily K
AU  - Phillips EK
AD  - Stead Family Department of Pediatrics, Medical Genetics, University of Iowa 
      Hospitals and Clinics, Iowa City, IA, USA.
FAU - Calhoun, Amy R U L
AU  - Calhoun ARUL
AD  - Stead Family Department of Pediatrics, Medical Genetics, University of Iowa 
      Hospitals and Clinics, Iowa City, IA, USA.
LA  - eng
GR  - n/a/Iowa Ladies Football Academy/
PT  - Journal Article
DEP - 20190205
PL  - Germany
TA  - J Community Genet
JT  - Journal of community genetics
JID - 101551501
PMC - PMC6754489
OTO - NOTNLM
OT  - Case definitions
OT  - Diagnostic testing
OT  - Molecular testing
OT  - Newborn screening
OT  - VLCAD
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/02/06 06:00
MHDA- 2019/02/06 06:01
PMCR- 2019/10/01
CRDT- 2019/02/06 06:00
PHST- 2018/08/01 00:00 [received]
PHST- 2019/01/22 00:00 [accepted]
PHST- 2019/02/06 06:00 [pubmed]
PHST- 2019/02/06 06:01 [medline]
PHST- 2019/02/06 06:00 [entrez]
PHST- 2019/10/01 00:00 [pmc-release]
AID - 10.1007/s12687-019-00409-8 [pii]
AID - 409 [pii]
AID - 10.1007/s12687-019-00409-8 [doi]
PST - ppublish
SO  - J Community Genet. 2019 Oct;10(4):447-451. doi: 10.1007/s12687-019-00409-8. Epub 
      2019 Feb 5.