In 2015, Pompe disease became the first lysosomal storage disorder to be recommended for universal newborn screening by the Secretary of the U.S. Department of Health and Human Services. Newborn screening for Pompe has been implemented in 20 states and several countries across the world. The rates of later-onset disease phenotypes for Pompe and pseudodeficiency alleles are higher than initially anticipated, and these factors must be considered during Pompe disease newborn screening. This report presents an overview of six years of data from the Missouri State Public Health Laboratory for Pompe disease newborn screening and follow-up.Enzyme-based newborn screening for Mucopolysaccharidosis type I (MPS I) has a high false-positive rate due to the prevalence of pseudodeficiency alleles, often resulting in unnecessary and costly follow up. The glycosaminoglycans (GAGs), dermatan sulfate (DS) and heparan sulfate (HS) are both substrates for α-l-iduronidase (IDUA). These GAGs are elevated in patients with MPS I and have been shown to be promising biomarkers for both primary and second-tier testing. Since February 2016, we have measured DS and HS in 1213 specimens submitted on infants at risk for MPS I based on newborn screening. Molecular correlation was available for 157 of the tested cases. Samples from infants with MPS I confirmed by IDUA molecular analysis all had significantly elevated levels of DS and HS compared to those with confirmed pseudodeficiency and/or heterozygosity. Analysis of our testing population and correlation with molecular results identified few discrepant outcomes and uncovered no evidence of false-negative cases. We have demonstrated that blood spot GAGs analysis accurately discriminates between patients with confirmed MPS I and false-positive cases due to pseudodeficiency or heterozygosity and increases the specificity of newborn screening for MPS I.The California Department of Public Health started universal newborn screening for Pompe disease in August 2018 with a two-tier process including (1) acid alpha-glucosidase (GAA) enzyme activity assay followed by, (2) GAA gene sequencing analysis. This study examines results from the first year of screening in a large and diverse screening population. With 453,152 screened newborns, the birth prevalence and GAA enzyme activity associated with various types of Pompe disease classifications are described. The frequency of GAA gene mutations and allele variants are reported. Of 88 screen positives, 18 newborns were resolved as Pompe disease, including 2 classic infantile-onset and 16 suspected late-onset form. The c.-32-13T>G variant was the most common pathogenic mutation reported. African American and Asian/Pacific Islander newborns had higher allele frequencies for both pathogenic and pseudodeficiency variants. After the first year of Pompe disease screening in California, the disease distribution in the population is now better understood. With the ongoing long-term follow-up system currently in place, our understanding of the complex genotype-phenotype relationships will become more evident in the future, and this should help us better understand the clinical significance of identified cases.This review summarises the trajectory of neonatal screening strategies for the detection of cystic fibrosis (CF) using the measurement of Immunoreactive Trypsin (IRT) in dried blood spots (DBS) from 1979 until the beginning of the 21st century when newborn screening (NBS) programmes started to spread throughout many countries, using IRT measurement combined with a CF genotype analysis of DBS.The positive predictive value of newborn screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency was less then 2% in New Zealand. This is despite a bloodspot second-tier immunoassay method for 17-hydroxyprogesterone measurement with an additional solvent extract step to reduce the number of false positive screening tests. We developed a liquid chromatography tandem mass spectrometry (LCMSMS) method to measure 17-hydroxyprogesterone in bloodspots to replace our current second-tier immunoassay method. The method was assessed using reference material and residual samples with a positive newborn screening result. Correlation with the second-tier immunoassay was determined and the method was implemented. Newborn screening performance was assessed by comparing screening metrics 2 years before and 2 years after LCMSMS implementation.  https://www.selleckchem.com/products/jh-x-119-01.html  Screening data analysis demonstrated the number of false positive screening tests was reduced from 172 to 40 in the 2 years after LCMSMS implementation. The positive predictive value of screening significantly increased from 1.71% to 11.1% (X2 test, p less then 0.0001). LCMSMS analysis of 17OHP as a second-tier test significantly improves screening specificity for CAH due to 21-hydroxylase deficiency in New Zealand.Statewide newborn screening for Pompe disease began in Illinois in 2015. As of 30 September 2019, a total of 684,290 infants had been screened and 395 infants (0.06%) were screen positive. A total of 29 cases of Pompe disease were identified (3 infantile, 26 late-onset). While many of the remainder were found to have normal alpha-glucosidase activity on the follow-up testing (234 of 395), other findings included 62 carriers, 39 infants with pseudodeficiency, and eight infants who could not be given a definitive diagnosis due to inconclusive follow-up testing.Pompe disease (PD) is a rare, autosomal-recessively inherited deficiency in the enzyme acid α-glucosidase. It is a spectrum disorder; age at symptom onset and rate of deterioration can vary considerably. In affected infants prognosis is poor, such that without treatment most infants die within the first year of life. To lose a baby in their first year of life to a rare disease causes much regret, guilt, and loneliness to parents, family, and friends. To lose a baby needlessly when there is an effective treatment amplifies this sadness. With so little experience of rare disease in the community, once a baby transfers to their home they are subject to a very uncertain and unyielding diagnostic journey while their symptomology progresses and their health deteriorates. With a rare disease like PD, the best opportunity to diagnose a baby is at birth. PD is not yet included in the current newborn screening (NBS) panel in Australia. Should it be? In late 2018 the Australian Pompe Association applied to the Australian Standing committee on Newborn Screening to have PD included.