Newborn Screening for Galactosemia: A Review of 5 Years of Data and Audit of a Revised Reporting Approach

Abstract

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 × 106 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 ≥1.110 mmol/L (≥20 mg/dL). The positive predictive value of a GALT cutoff of ≤40 μmol/L was 83%. After a protocol change that redefined a critical result as a GALT value ≤40 μmol/L and/or a Gal value ≥1.665 mmol/L (≥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 ≤40 μmol/L/L and a Gal cutoff of ≥1.665 mmol/L (≥30 mg/dL) for urgent notification/referral dramatically reduces false positives and unnecessary follow-up, thereby reducing the stress on healthcare resources.

A case of galactosemia misdiagnosed as cow’s milk intolerance

“…The galactose-1-phosphate uridyltransferase assay for newborn screening [19] would prevent misdiagnoses in patients affected by galactosemia. Unfortunately a screening program for this disorder is not available in all countries.…”

Newborn Screening for Galactosemia in the United States: Looking Back, Looking Around, and Looking Ahead

“…Some states also measured total galactose (galactose + galactose-1-phosphate); however, some measured total galactose in all samples (e.g., SC) while others measured total galactose only in samples already flagged by a borderline, low, or absent GALT activity level (e.g., GA, MI, NY, OH). Further, not every state that measured total galactose used that information in the Note: Testing strategies used by specific labs may change over time; these are the responses received at the time requested (2011-2012) a GALT activity was measured using a coupled assay that produced NADPH so that mM NADPH produced in a given period of time corresponded to a given level of GALT activity in the sample (Freer et al 2010)) decision of whether or not to flag a sample as abnormal for galactosemia, and some states also had a special approach to NBS if the baby had been transfused prior to sample collection.…”

“…For example, Georgia detected close to 20 DG cases per 100,000 newborns screened, while Mississippi detected a median of fewer than 5. This difference likely reflects, at least in part, the differing GALT cutoff levels used by the two states: in Georgia a sample showing <60 mM (NADPH) (Freer et al 2010) GALT activity was defined as abnormal, whereas in Mississippi a sample needed to show <40 mM (NADPH) GALT activity to be declared abnormal (Table 2).…”

Stopping Parenteral Nutrition for 3 Hours Reduces False Positives in Newborn Screening

“…6,9,[19][20][21][22][23] This study shows a new NBS blood collection, the 3-hour stop-PN protocol, can significantly reduce falsepositive AA results and the associated medical costs. The current study confirms and expands the results of a smaller study of the effect of holding AA containing PN by Morris et al 23 The current study includes a much larger sample size of VLBW infants (87 vs 413 in this study).…”