Abstract
INTRODUCTION: There is limited understanding of relationships between genotype, phenotype and other conditions contributing to health in neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) identified through newborn screening. METHODS: Retrospective analysis of comprehensive data from a cohort of 221 newborn-screened subjects identified as affected with MCADD in the Inborn Errors of Metabolism - Information System (IBEM-IS), a long term follow-up database of the Inborn Errors of Metabolism Collaborative, was performed. RESULTS: The average age at notification of first newborn screen results to primary care or metabolic providers was 7.45days. The average octanoylcarnitine (C8) value on first newborn screen was 11.2μmol/L (median 8.6, range 0.36-43.91). A higher C8 level correlated with an earlier first subspecialty visit. Subjects with low birth weight had significantly lower C8 values. Significantly higher C8 values were found in symptomatic newborns, in newborns with abnormal lab testing in addition to newborn screening and/or diagnostic tests, and in subjects homozygous for the c.985A>G ACADM gene mutation or compound heterozygous for the c.985A>G mutation and deletions or other known highly deleterious mutations. Subjects with neonatal symptoms, or neonatal abnormal labs, or neonatal triggers were more likely to have at least one copy of the severe c.985A>G ACADM gene mutation. C8 and genotype category were significant predictors of the likelihood of having neonatal symptoms. Neonates with select triggers were more likely to have symptoms and laboratory abnormalities. CONCLUSIONS: This collaborative study is the first in the United States to describe health associations of a large cohort of newborn-screened neonates identified as affected with MCADD. The IBEM-IS has utility as a platform to better understand the characteristics of individuals with newborn-screened conditions and their follow-up interactions with the health system.