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

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.

Analysis of mRNA partitioning between the cytosol and endoplasmic reticulum compartments of mammalian cells.

All eukaryotic cells display a dramatic partitioning of mRNAs between the cytosol and endoplasmic reticulum (ER) compartments-mRNAs encoding secretory and integral membrane proteins are highly enriched on ER-bound ribosomes and mRNAs encoding cytoplasmic/nucleoplasmic proteins are enriched on cytosolic ribosomes. In current views, this partitioning phenomenon occurs through positive selection-mRNAs encoding signal sequence-bearing proteins are directed into the signal recognition particle pathway early in translation and trafficked as mRNA/ribosome/nascent polypeptide chain complexes to the ER. In the absence of an encoded signal sequence, mRNAs undergo continued translation on cytosolic ribosomes. Recent genome-wide analyses of mRNA partitioning between the cytosol and the ER compartments have identified subsets of mRNAs that are non-canonically partitioned to the ER-although lacking an encoded signal sequence, they are translated on ER-bound ribosomes. These findings suggest that multiple, and as yet unidentified, pathways exist for directing mRNA partitioning in the cell. In this contribution, we briefly review the literature describing the subcellular partitioning patterns of mRNAs and present a detailed methodology for studying this fundamental, yet poorly understood process.