Newborn screening for galactosemia: a review of 5 years of data and audit of a revised reporting approach.
BACKGROUND
Availability of the galactose-1-phosphate uridyltransferase (GALT) assay for newborn (NB) screening has improved identification of classic galactosemia. Previously defined critical cutoffs for total galactose (Gal), typically 1.110 mmol/L (20 mg/dL), are still in use in laboratories measuring total Gal for the diagnosis of nonclassic galactosemias. Urgent notification/referral to a treatment center follows, although few of the NBs will need treatment.


METHODS
We reviewed all NB galactosemia-screening results and their corresponding clinical outcomes over a 5-year period (first phase, 1.32 x 10(6) NBs) and then over a 2-year period (second phase, 274 960 NBs). Each NB was screened for Gal and GALT. When Gal was increased and/or GALT was deficient, testing for percentage galactose-1-phosphate and/or DNA testing for common GALT mutations were performed.


RESULTS
Of 209 reported positive results, 89% did not indicate GALT deficiency. These non-GALT-deficient results represented mostly clinically benign cases with a Gal threshold of > or = 1.110 mmol/L (> or = 20 mg/dL). The positive predictive value of a GALT cutoff of < or = 40 micromol/L was 83%. After a protocol change that redefined a critical result as a GALT value < or = 40 micromol/L and/or a Gal value > or = 1.665 mmol/L (> or = 30 mg/dL), results were monitored for an additional 2 years. The new protocol dramatically reduced the number of urgent calls/referrals and reduced the total number of referrals by nearly half.


CONCLUSIONS
Use of a GALT cutoff of < or = 40 micromol/L/L and a Gal cutoff of > or = 1.665 mmol/L (> or = 30 mg/dL) for urgent notification/referral dramatically reduces false positives and unnecessary follow-up, thereby reducing the stress on healthcare resources.
Freer
Dennis E
DE
PerkinElmer Genetics, Inc., 90 Emerson Lane, Bridgeville, PA 15017, USA. Dennis.Freer@perkinelmer.com
Ficicioglu
Can
C
Finegold
David
D
D004247:DNA / Q000235:genetics; D005690:Galactose / Q000097:blood; D005693:Galactosemias / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D015997:Neonatal Screening / Q000379:methods*; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000097:blood / Q000235:genetics
D004247:DNA; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase; D005690:Galactose