ABCMdb

PMID: 20521170

Hale JE, Parad RB, Dorkin HL, Gerstle R, Lapey A, O'Sullivan BP, Spencer T, Yee W, Comeau AM
Cystic fibrosis newborn screening: using experience to optimize the screening algorithm.
J Inherit Metab Dis. 2010 Oct;33(Suppl 2):S255-61. Epub 2010 Jun 3., [PubMed]

Sentences

No. Mutations Sentence Comment

47 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Gly542* ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Arg75Gln ABCC7 p.Asp828Gly Extensive follow-up Table 1 Children who are followed at a cystic fibrosis (CF) center who were not identified by CF newborn screening (NBS) Presentation Status at last update NBS IRT%, age at dx Genotype Sweat [Cl- ] (MEq/L)a Five CF infants with false-negative CF NBS results FTT, upper respiratory infections, chronic cough Pancreatic sufficient, sinus disease, positive cultures for Staph. aureus and H. flu 84.2%, 3 months DF508/R117H 67 Meconium ileus 93.9%, birth G542X / unknown 57.7, 67.4 FTT, recurrent pneumonia, asthma 62.3%, 4 years D828G / 3271+18 C or T 62 Asthma 78.6%, 3 years D1270N / R74W 86.5 Chronic cough and sinusitis 74.1%, 4 years R75Q / unknown (second mutation not identified by sequencing) 82, 68 Four additional infants followed at CF center who do not (yet) carry a CF diagnosis Chronic cough Pancreatic sufficient, asthma, moderate Staph. aureus and H. flu 39.7%, 5 years DF508 / unknown 39 Chronic cough; sweat-tested and genotyped after parents found to be carriers during pregnancy with younger sibling Does not carry CF diagnosis, pancreatic sufficient, exercise-induced asthma, normal PFTs, cultures Staph. aureus 94.6%, 3 years DF508/R117H 56 Two siblings who are well; genotyped for family history Positive cultures for Staph. aureus and H.flu 21.3%, 71.2% (sib) DF508 / R117H 20, not done IRT Immunoreactive trypsinogen, FTT failure to thrive, PFT pulmonary function test a Value(s) reported from independent visits of infants with positive CF NBS results has allowed the MA CF NBS program to incorporate communication of relative risk of CF following a positive NBS result that is based upon combined consideration (multi-analyte profiling) of both the IRT concentration and the screening-genotype results. Login to comment 72 ABCC7 p.Pro67Leu The fourth infant had a sweat chloride that was in the borderline range (38 mEq/L) and has a genotype that can be associated with a variable phenotype (P67L/5T). Login to comment 77 ABCC7 p.Gly85Glu ABCC7 p.Pro67Leu ABCC7 p.Arg117Cys Discussion In addition to providing the laboratory services necessary for implementation of CF NBS, effective newborn screen- Table 4 Summary of positive screens identified by Massachusetts failsafe cystic fibrosis (CF) newborn screening (NBS) protocol Top 0.2% [IRT] Top 0.1% [IRT] Total Monitored by CF center 3 1 4 Borderline sweat testa 1 1 2 Negative sweat test 364 136 485 Not sweat testedb 91 62 153 IRT Immunoreactive trypsinogen a Infants do not have CF and are not monitored by a CF center b The 153 infants who did not have a documented sweat test either expired prior to a sweat test (36%), had a QNS sweat test and did not return for repeat sweat test (8%), had parents who refused sweat test (2%), or are lost to follow up (54%) Table 5 Infants followed at a cystic fibrosis (CF) center identified by Massachusetts failsafe CF newobrn screening (NBS) protocol Infant [IRT] (ng/ml) Mutations on NBS panel (n) Sweat [Cl- ] MEq/L Extended genotype results Comments A 141 16 41, 83 G85E/R117C Would be identified by current mutation panel B 503 16 103 Negative for 86 CFTR mutations C 274 16 92 Negative for 86 CFTR mutations D 159 39 38 P67L trans to 5t Does not meet 2008 CFF consensus guidelines for CF but is positive for CRMS CFF Cystic Fibrosis Foundation, CRMS cystic fibrosis transmembrane conductance regulator-related metabolic syndrome (Borowitz 2009) ing programs should collect and monitor outcomes for quality assurance purposes. Login to comment