2023 APHL/ISNS Newborn Screening Symposium.

Introduction and Abstracts of the 2023 APHL/ISNS Newborn Screening Symposium in Sacramento, CA, USA from 15-19 October 2023.

First Three Years' Experience of Mucopolysaccharidosis Type-I Newborn Screening in California.

Objective: To report on the first 3 years of mucopolysaccharidosis type I (MPS I) newborn screening (NBS) in the large and diverse state of California.

Study Design: The California Genetic Disease Screening Program began universal NBS for MPS I on August 29, 2018. The screening uses a 2-tiered approach: an α-L-iduronidase (IDUA) enzyme activity assay followed by DNA sequencing for variants in the IDUA gene.

California's experience with SMA newborn screening: A successful path to early intervention.

Background: Universal spinal muscular atrophy (SMA) newborn screening was implemented in California on June 24, 2020.

Objective: We describe California's experience with the first 18 months of SMA newborn screening, including our assay methodology, timeliness of screening and follow-up milestones, and clinical and epidemiological outcomes observed.

Methods: Dried blood spots are screened for SMA using multiplex real time polymerase chain reaction (RT-PCR) to detect deletions of exon 7 in the survival of motor neuron 1 (SMN1) gene.

Collagen X Marker Levels are Decreased in Individuals with Achondroplasia.

Collagen X marker (CXM) is a degradation fragment of collagen type X. It is a real-time biomarker of height velocity with established norms. Plasma C-type natriuretic peptide (CNP) and NTproCNP levels have also been found to correlate with growth velocity in the general population and are elevated in individuals with achondroplasia compared with age- and sex-matched controls.

Progression of PTH Resistance in Autosomal Dominant Pseudohypoparathyroidism Type Ib Due to Maternal STX16 Deletions.

Context: Maternally inherited STX16 deletions that cause loss of methylation at GNAS exon A/B and thereby reduce Gsα expression are the most frequent cause of autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP1B). Early identification of these disease-causing variants in the children of affected and unaffected female carriers would prompt treatment with calcium and calcitriol once parathyroid hormone (PTH) levels increase, thereby preventing hypocalcemia and associated complications.

Objective: This study aimed to determine when PTH and calcium abnormalities develop after birth if a STX16 deletion is inherited maternally.

Alterations of a serum marker of collagen X in growing children with osteogenesis imperfecta.

Abnormalities in the structure and/or processing of type I collagen cause osteogenesis imperfecta and result in bone fragility, abnormal bone growth and short stature. Type I collagen is expressed in the growth plate but the mechanisms by which abnormalities in collagen I contribute to growth plate dysfunction and growth retardation are unknown. The non-collagenous domain (NC1) of type X collagen (CXM) is released from the hypertrophic zone of active growth plates and is a marker for new endochondral bone formation.

Adrenoleukodystrophy Newborn Screening in California Since 2016: Programmatic Outcomes and Follow-Up.

X-linked adrenoleukodystrophy (ALD) is a recent addition to the Recommended Uniform Screening Panel, prompting many states to begin screening newborns for the disorder. We provide California's experience with ALD newborn screening, highlighting the clinical and epidemiological outcomes observed as well as program implementation challenges. In this retrospective cohort study, we examine ALD newborn screening results and clinical outcomes for 1,854,631 newborns whose specimens were received by the California Genetic Disease Screening Program from 16 February 2016 through 15 February 2020.

The First Year Experience of Newborn Screening for Pompe Disease in California.

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) 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.

Norms for Clinical Use of CXM, a Real-Time Marker of Height Velocity.

Context: Height velocity (HV) is difficult to assess because growth is very slow. The current practice of calculating it from measurements taken at several-month intervals is insufficient for managing children with growth disorders. We identified a bone growth by-product (collagen X biomarker, CXM) in blood that in preliminary analysis in healthy children correlated strongly with conventionally determined HV and displayed a pattern resembling published norms for HV vs age.

Association between maternal periconceptional alcohol consumption and neural tube defects: Findings from the National Birth Defects Prevention Study, 1997-2011.

Background: Neural tube defects (NTD)s are common birth defects with a multifactorial etiology. Findings from human studies examining environmental (non-inherited) exposures tend to be inconclusive. In particular, although animal studies of alcohol exposure and NTDs support its teratogenic potential, human studies are equivocal.

Changes in Manufacturing Processes of Biologic Therapies Can Alter the Immunogenicity Profile of the Product.

Manufacturing process changes may alter the characteristics of a protein therapeutic. In 2009, somatropin (version 1.0), a recombinant human growth hormone therapeutic, underwent a manufacturing update (version 1.

Evaluating RANKL and OPG levels in patients with Duchenne muscular dystrophy.

Unlabelled: RANKL-OPG should be explored in DMD patients to potentially provide targeted therapy. We quantified RANKL and OPG levels in DMD patients compared with controls. RANKL, OPG, and RANKL:OPG significantly declined with age in DMD patients suggesting some bone turnover markers are difficult to assess or use as therapeutic indicators.

Quantifying RANKL and OPG levels in healthy children: A large cross-sectional analysis.

Background: There have been new advances in understanding bone remodeling on a molecular level including the RANKL-OPG pathway, leading to advancements in targeted therapeutic intervention. There is however limited data in pediatrics with little known on normative values in healthy children. This is the largest cohort to quantify RANKL, OPG, and RANKL: OPG levels in healthy children as well as study the influence of age, gender, Tanner stage, and BMI in this population.

Plasma C-Type Natriuretic Peptide: Emerging Applications in Disorders of Skeletal Growth.

Although studies in experimental animals show that blood levels of C-type natriuretic peptide (CNP) and its bioinactive aminoterminal propeptide (NTproCNP) are potential biomarkers of long bone growth, a lack of suitable assays and appropriate reference ranges has limited the application of CNP measurements in clinical practice. Plasma concentrations of the processed product of proCNP, NTproCNP - and to a lesser extent CNP itself - correlate with concurrent height velocity throughout all phases of normal skeletal growth, as well as during interventions known to affect skeletal growth in children. Since a change in levels precedes a measurable change in height velocity during interventions, measuring NTproCNP may have predictive value in clinical practice.

Pitfalls with Vitamin D Research in Musculoskeletal Disorders and Recommendations on How to Avoid Them.

Reports suggesting that vitamin D may have extraskeletal roles have renewed interest in vitamin D research and stimulated publication of an increasing number of new studies each year. These studies typically assess vitamin D status by measuring the blood concentration of 25-hydroxyvitamin D [25(OH)D], the principal circulating metabolite of vitamin D. Unfortunately, variations in assay format, inconsistency in interpreting 25(OH)D concentrations, cohort bias (age, body mass index, race, season of measurements etc.

A systematic exploration of [Formula: see text] cutoff ranges in machine learning models for protein mutation stability prediction.

Discerning how a mutation affects the stability of a protein is central to the study of a wide range of diseases. Mutagenesis experiments on physical proteins provide precise insights about the effects of amino acid substitutions, but such studies are time and cost prohibitive. Computational approaches for informing experimentalists where to allocate wet-lab resources are available, including a variety of machine learning models.

Dynamic response of C-type natriuretic peptide and its aminoterminal propeptide (NTproCNP) to growth hormone treatment in children with short stature.

Objective: C-type natriuretic peptide (CNP) and its aminoterminal propeptide (NTproCNP) are potential biomarkers of recombinant human growth hormone (rhGH) efficacy. The objective of this study was to describe the pharmacodynamics of plasma CNP and NTproCNP levels in response to rhGH treatment and to identify the optimal time of sampling after starting rhGH.

Design: This was a prospective, observational study.

Development and implementation of the first national data quality standards for population-based birth defects surveillance programs in the United States.

Background: Population-based birth defects surveillance is a core public health activity in the United States (U.S.); however, the lack of national data quality standards has limited the use of birth defects surveillance data across state programs.

State Legislation, Regulations, and Hospital Guidelines for Newborn Screening for Critical Congenital Heart Defects - United States, 2011-2014.

Critical congenital heart defects (CCHD) occur in approximately two of every 1,000 live births. Newborn screening provides an opportunity for reducing infant morbidity and mortality. In September 2011, the U.

Detection of critical congenital heart defects: Review of contributions from prenatal and newborn screening.

In 2011, statewide newborn screening programs for critical congenital heart defects began in the United States, and subsequently screening has been implemented widely. In this review, we focus on data reports and collection efforts related to both prenatal diagnosis and newborn screening. Defect-specific, maternal, and geographic factors are associated with variations in prenatal detection, so newborn screening provides a population-wide safety net for early diagnosis.

Next steps for birth defects research and prevention: The birth defects study to evaluate pregnancy exposures (BD-STEPS).

Background: The Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS) is a population-based, multi-Center case-control study of modifiable risk factors for selected birth defects in the United States. BD-STEPS is the second major research effort of the Centers for Birth Defects Research and Prevention, which extends and expands the initial research effort, the National Birth Defects Prevention Study (NBDPS).

Methods: BD-STEPS focuses on 17 categories of structural birth defects selected based on severity, prevalence, consistent ascertainment, and previous findings that warrant additional research.

Factors associated with high hospital resource use in a population-based study of children with orofacial clefts.

Background: Little is known about population-based maternal, child, and system characteristics associated with high hospital resource use for children with orofacial clefts (OFC) in the US.

Methods: This was a statewide, population-based, retrospective observational study of children with OFC born between 1998 and 2006, identified by the Florida Birth Defects Registry whose records were linked with longitudinal hospital discharge records. We stratified the descriptive results by cleft type [cleft lip with cleft palate, cleft lip, and cleft palate] and by isolated versus nonisolated OFC (accompanied by other coded major birth defects).