Organic Acidemias: Clinical Presentation in Neonates

Abstract

Organic acidemias (OAs) are heritable genomic abnormalities characterized by the absence or defects in critical enzyme(s), which result in the accumulation of abnormal and toxic organic acid metabolites. These metabolites can be detected in blood and/or urine in high levels. Organic acidemias can have severe clinical manifestations, where most patients become symptomatic within the neonatal period or early infancy. Mildly affected cases may present later during adolescence or adulthood following decompensation during illness, following surgery, or with prolonged fasting. Acute clinical presentations include liver failure, lethargy, altered sensorium (encephalopathy), and/or seizures in the acute phase; subacute/delayed manifestations may include failure to thrive, developmental delay, and/or cardiomyopathy. In neonates, differential diagnoses include sepsis, metabolic disturbances, and intracranial bleeding. A high index of suspicion is essential for early, timely diagnosis. This article seeks to provide consolidated information on OAs, including pathogenesis, clinical presentation, diagnosis, and contemporary management.