Related Experiment Video
Updated: Mar 17, 2026
Quantification of Coenzyme A in Cells and Tissues
Published on: September 27, 2019
221 newborn-screened neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency: Findings from the Inborn
Kristi Bentler1, Shaohui Zhai2, Sara A Elsbecker3
1Minnesota Department of Health, St. Paul, MN, United States.
Insights
Newborn screening for medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) shows genotype and C8 levels predict neonatal symptoms. This study highlights the utility of the Inborn Errors of Metabolism - Information System (IBEM-IS) for understanding MCADD health associations.
Area of Science:
- Biochemistry
- Genetics
- Neonatal Medicine
Background:
- Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is a genetic disorder affecting fatty acid metabolism.
- Understanding genotype-phenotype correlations in MCADD is crucial for neonates identified through newborn screening.
Purpose of the Study:
- To investigate the relationships between genotype, phenotype, and health outcomes in neonates with MCADD.
- To assess the utility of the Inborn Errors of Metabolism - Information System (IBEM-IS) for studying newborn-screened conditions.
Main Methods:
- Retrospective analysis of data from 221 newborn-screened MCADD subjects in the IBEM-IS database.
- Correlation of octanoylcarnitine (C8) levels and ACADM gene mutations with clinical presentation and laboratory findings.
Main Results:
- Higher C8 levels correlated with earlier subspecialty visits and were found in symptomatic newborns and those with severe ACADM gene mutations.
- Neonatal symptoms, abnormal labs, and specific ACADM mutations (c.985A>G) were associated with increased risk.
- C8 levels and genotype were significant predictors of neonatal symptoms.
Conclusions:
- This study provides the first comprehensive description of health associations in a large US cohort of newborn-screened MCADD neonates.
- The IBEM-IS serves as a valuable platform for understanding characteristics and healthcare interactions of individuals with newborn-screened conditions.
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.
More Related Videos
06:53Visualization of Mitochondrial Respiratory Function using Cytochrome C Oxidase / Succinate Dehydrogenase COX/SDH Double-labeling Histochemistry
Published on: November 23, 2011
03:19Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Related Concept Videos
01:28Overview of Fatty Acid Metabolism
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
01:35Loss of Carboxy Group as CO2: Decarboxylation of Malonic Acid Derivatives
01:15Pyruvate Oxidation
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
01:02Loss of Carboxy Group as CO2: Decarboxylation of β-Ketoacids
01:25Lipid Catabolism
01:24Phase II Reactions: Acetylation Reactions
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...