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. 2015:15:79-93.
doi: 10.1007/8904_2014_302. Epub 2014 Apr 10.

Newborn screening for galactosemia in the United States: looking back, looking around, and looking ahead

Brook M Pyhtila  1 , Kelly A Shaw, Samantha E Neumann, Judith L Fridovich-Keil
Affiliations

Newborn screening for galactosemia in the United States: looking back, looking around, and looking ahead

Brook M Pyhtila et al. JIMD Rep. 2015.

Erratum in

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.

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Figures

Fig. 1
Fig. 1
The Leloir Pathway of galactose metabolism. Classic galactosemia results from profound loss of galactose-1P uridylyltransferase (GALT); Duarte galactosemia results from partial loss of GALT. Profound loss of GALK leads to galactokinase deficiency galactosemia, and partial loss of GALE results in generalized, intermediate, or peripheral epimerase deficiency galactosemia depending on the degree of impairment and the tissues impacted
Fig. 2
Fig. 2
Classic, Duarte, and false positive rates from galactosemia newborn screening in respondent states. (a) Detection rates for classic galactosemia per 100,000 newborns screened. (b) Detection rates for Duarte galactosemia per 100,000 newborns screened. We were not able to calculate a DG detection rate for Indiana. (c) False positive rates defined as the total number of positive galactosemia screening results minus the numbers of cases diagnosed with classic, variant, or Duarte galactosemia. We were not able to calculate false positive rates for Indiana or Mississippi. The number of years of data included in the analysis for each box and whisker plot is indicated in parentheses above the box. For each plot the lower, middle, and upper boundaries of the box represent the 25th, 50th, and 75th percentiles for the data set, respectively, and the whiskers indicate the full range of the data. The 25th, 50th, and 75th percentile limits for each population plotted in Fig. 2 are also presented in Supplementary Table 2
Fig. 3
Fig. 3
GALT activity levels detected in hemolysates from infants in different diagnostic categories for galactosemia. GALT activity levels determined as part of follow-up testing at the Emory Genetics Lab (EGL) were ascertained via a HIPAA waiver and presented as box-and-whisker plots by diagnostic group. The upper, middle, and lower boundaries of each box indicate the 25th, 50th, and 75th percentiles of the data set, respectively; the whiskers indicate the full range of the data, and the cross hatches in the upper and lower whiskers indicate the 90th and 10th percentiles of the data set, respectively. The number of points in each data set is indicated in parentheses above the box
Fig. 4
Fig. 4
Gal-1P levels detected in hemolysates from infants in different diagnostic categories for galactosemia. Gal-1P levels determined as part of follow-up testing at the Emory Genetics Lab (EGL) were ascertained via a HIPAA waiver and presented as box-and-whisker plots by diagnostic group. The lower, middle, and upper boundaries of each box indicate the 25th, 50th, and 75th percentiles of the data set, respectively; the whiskers indicate the full range of the data, and the cross hatches in the upper and lower whiskers indicate the 90th and 10th percentiles of the data set, respectively. The number of points in each data set is indicated in parentheses above the box
Fig. 5
Fig. 5
Relationship between Gal-1P and GALT activity levels detected on follow-up testing of hemolysates from infants with classic or Duarte galactosemia. GALT activity and Gal-1P levels determined as part of follow-up testing at the Emory Genetics Lab (EGL) were ascertained via a HIPAA waiver and presented as “scatter plots.” The highest gal-1P levels were all found in infants with undetectable GALT activity, but there was also considerable scatter in both diagnostic groups
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