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

Abstract

It has been 50 years since the first newborn screening (NBS) test for galactosemia was conducted in Oregon, and almost 10 years since the last US state added galactosemia to their NBS panel. During that time an estimated >2,500 babies with classic galactosemia have been identified by NBS. Most of these infants were spared the trauma of acute disease by early diagnosis and intervention, and many are alive today because of NBS. Newborn screening for galactosemia is a success story, but not yet a story with a completely happy ending. NBS, follow-up testing, and intervention for galactosemia continue to present challenges that highlight gaps in our knowledge. Here we compare galactosemia screening and follow-up data from 39 NBS programs gathered from the states directly or from public sources. On some matters the programs agreed: for example, those providing relevant data all identify classic galactosemia in close to 1/50,000 newborns and recommend immediate and lifelong dietary restriction of galactose for those infants. On other matters the programs disagree. For example, Duarte galactosemia (DG) detection rates vary dramatically among states, largely reflecting differences in screening approach. For infants diagnosed with DG, >80% of the programs surveyed recommend complete or partial dietary galactose restriction for the first year of life, or give mixed recommendations; <20% recommend no intervention. This disparity presents an ongoing dilemma for families and healthcare providers that could and should be resolved.

False-Positive Newborn Screen Using the Beutler Spot Assay for Galactosemia in Glucose-6-Phosphate Dehydrogenase Deficiency

“…Several states use both measurements to screen for classical galactosemia. A study by Pyhtila et al looked at the testing strategies of state labs in the USA in 2011-2012 (Pyhtila et al 2014b). Of the 19 states that responded, 40% exclusively used GALT, 40% used GALT plus total galactose, and 20% only used total galactose if the GALT was low.…”

Acute and long-term outcomes in a Drosophila melanogaster model of classic galactosemia occur independently of galactose-1-phosphate accumulation

“…Newborn screening for galactosemia coupled with rapid dietary restriction of galactose has saved the lives of thousands of infants born with CG in the United States in the past 50 years (Pyhtila et al, 2015). However, the long-term outcomes of those infants with CG who do survive remain challenging and uncertain, in large part because we still do not fully understand the pathophysiology of this disease.…”

Developmental Outcomes of School-Age Children with Duarte Galactosemia: A Pilot Study

“…Duarte galactosemia (DG) affects an estimated 1/4,000 live births every year in the United States (USA) (Fernhoff 2010;Pyhtila et al 2014); this is close to 10 times the number who are affected by classic galactosemia (CG). Unlike the potentially lethal CG, which results from profound loss of galactose-1-P uridylyltransferase (GALT), DG occurs in patients who are compound heterozygotes for one mild (D or D2) and one severe (G) allele of GALT.…”

“…Most infants diagnosed with DG in the USA come to clinical attention because of an abnormal newborn screening (NBS) result for galactosemia (Pyhtila et al 2014). Median detection rates for DG vary widely among US states, from essentially zero to more than 1/3,500 births; this range is believed to reflect differences in screening protocol rather than actual differences in prevalence (Pyhtila et al 2014).…”

“…Median detection rates for DG vary widely among US states, from essentially zero to more than 1/3,500 births; this range is believed to reflect differences in screening protocol rather than actual differences in prevalence (Pyhtila et al 2014). Whether NBS should be used to identify DG infants, and whether DG infants benefit from early detection and dietary restriction of galactose in infancy, which is the practice in some states, remains unclear; doctors and public health professionals remain divided on the issue (Fernhoff 2010;Pyhtila et al 2014).…”