, Melissa Yssel, MB ChB, FC Path(SA) Chem 139, and Wendy M. Zakowicz, BS 79 Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. Methods: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration.

Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency can present at various ages from the neonatal period to adulthood, and poses the greatest risk of complications during intercurrent illness or after prolonged fasting. Early diagnosis, treatment, and surveillance can reduce mortality; hence, the disorder is included in the newborn Recommended Uniform Screening Panel (RUSP) in the United States. The Inborn Errors of Metabolism Information System (IBEM-IS) was established in 2007 to collect longitudinal information on individuals with inborn errors of metabolism included in newborn screening (NBS) programs, including VLCAD deficiency. We retrospectively analyzed early outcomes for individuals who were diagnosed with VLCAD deficiency by NBS and describe initial presentations, diagnosis, clinical outcomes and treatment in a cohort of 52 individuals ages 1–18 years. Maternal prenatal symptoms were not reported, and most newborns remained asymptomatic. Cardiomyopathy was uncommon in the cohort, diagnosed in 2/52 cases. Elevations in creatine kinase were a common finding, and usually first occurred during the toddler period (1–3 years of age). Diagnostic evaluations required several testing modalities, most commonly plasma acylcarnitine profiles and molecular testing. Functional testing, including fibroblast acylcarnitine profiling and white blood cell or fibroblast enzyme assay, is a useful diagnostic adjunct if uncharacterized mutations are identified.

Purpose Treatment of inherited metabolic disorders is accomplished by use of specialized diets employing medical foods and medically necessary supplements. Families seeking insurance coverage for these products express concern that coverage is often limited; the extent of this challenge is not well defined. Methods To learn about limitations in insurance coverage, parents of 305 children with inherited metabolic disorders completed a paper survey providing information about their use of medical foods, modified low-protein foods, prescribed dietary supplements, and medical feeding equipment and supplies for treatment of their child's disorder as well as details about payment sources for these products. Results Although nearly all children with inherited metabolic dis orders had medical coverage of some type, families paid “out of pocket” for all types of products. Uncovered spending was reported for 11% of families purchasing medical foods, 26% purchasing supplements, 33% of those needing medical feeding supplies, and 59% of families requiring modified low-protein foods. Forty-two percent of families using modified low-protein foods and 21% of families using medical foods reported additional treatment-related expenses of $100 or more per month for these products. Conclusion Costs of medical foods used to treat inherited metabolic disorders are not completely covered by insurance or other resources.

Introduction 3-Methyl crotonyl CoA carboxylase (3MCC) deficiency is an inborn error of leucine metabolism whose detection was increased with the advent of expanded newborn screening. While most NBS-identified infants appear clinically normal, prior studies suggest a possible increased risk for developmental or metabolic abnormalities. As yet, no predictive markers are known that can identify children at risk for biochemical or developmental abnormalities. Method All available 3-MCC cases diagnosed by newborn screening in the Inborn Errors of Metabolism Information System (IBEM-IS) were reviewed for markers that might be predictive of outcome. Results A limited number of cases were identified with traditional biochemical symptoms including acidosis, hyperammonemia or lactic acidosis, and 15% of those with available developmental information had recorded developmental disabilities not clearly attributable to other causes. There was no correlation between newborn screening (NBS) C5OH level and presence of metabolic, newborn, later-life or developmental abnormalities in these cases. Discussion This sample, obtained from the IBEM-IS database, attempts to avoid some of the ascertainment bias present in retrospective studies. An increase in developmental abnormalities and in traditionally described metabolic symptoms remains apparent, although no specific biochemical markers appear predictive of outcome. The role that prevention of fasting plays in outcome cannot be ascertained. These data suggest that C5OH level found on newborn screening by itself is not sufficient for diagnostic or predictive purposes.

Objective: To assess if vitamin A concentration in umbilical cord blood is associated with incidence and severity of respiratory infections in preschool Inuit children from Nunavik (Québec, Canada). Method: The medical charts of 305 children were reviewed from 0 to 5 years of age. The association between vitamin A concentration in umbilical cord plasma and the incidence rates of acute otitis media (AOM), lower respiratory tract infections (LRTIs) and hospitalization rates for LRTIs was evaluated using Poisson regression. Results: Compared to children with vitamin A concentration ≥20 μg/dl, adjusted rate ratios (RR) for children below 20 μg/dl ranged between 1.06-1.62 for AOM, 1.12-1.34 for LRTIs, and 1.09-1.43 for hospitalization for LRTIs. Most RRs were statistically significant for AOM and LRTIs, but not for hospitalization for LRTIs. Conclusion: Neonatal vitamin A deficiency appears to be a significant risk factor for AOM and LRTIs in this population.