NCC Knowledge Nugget Series: Propionic Acidemia ACT Sheet-Propionic Acidemia ACT Sheet

Propionic Acidemia ACT Sheet

Pdf Summary

The provided ACT Sheet is an educational resource for medical geneticists and clinicians, developed by the American College of Medical Genetics and Genomics (ACMG) and updated in September 2022. It focuses on assisting in the diagnosis and management of newborns with elevated C3 acylcarnitine, indicating potential propionic acidemia (PA) or methylmalonic acidemia (MMA). These conditions impede the body's ability to metabolize certain proteins and fats, posing severe toxicity risks shortly after birth.<br /><br />Key elements of the ACT Sheet include:<br />1. **Differential Diagnosis**: Lists possible conditions including PA, MMA, cobalamin (vitamin B12) absorption and processing disorders, maternal vitamin B12 deficiency, and succinate-CoA ligase deficiency.<br />2. **Condition Description**: PA results from defects in propionyl-CoA carboxylase, increasing propionate and C3 metabolite levels. MMA stems from methylmalonyl-CoA mutase deficiency or disruptions in vitamin B12 processing/transport, leading to elevated methylmalonate and C3 metabolites. Both conditions can manifest through acute neonatal symptoms like lethargy, vomiting, and metabolic acidosis.<br />3. **Immediate Actions**: Recommendations for clinicians include informing the family, assessing the newborn's clinical status, consulting a pediatric metabolic specialist, conducting confirmatory tests, initiating treatment, and documenting outcomes.<br />4. **Diagnostic Evaluation**: Describes necessary tests (plasma acylcarnitines, urine organic acids, plasma total homocysteine, plasma methylmalonic acid, molecular genetic testing) to differentiate between PA and MMA.<br />5. **Clinical Considerations**: PA and MMA require early and lifelong treatment; some MMA cases may respond to vitamin B12. Succinate-CoA ligase deficiency is noted as a rare condition.<br /><br />The sheet provides additional links to resources for emergency protocols, gene reviews, condition information for families, and directories for genetics clinics and genetic testing. It stresses the voluntary use of the resource, emphasizing clinicians should integrate their professional judgment and document rationale for deviating from suggested practices.

Keywords

ACT Sheet

medical genetics

ACMG

newborn screening

propionic acidemia

methylmalonic acidemia

elevated C3 acylcarnitine

diagnostic evaluation

immediate actions

clinical considerations