Propionic Acidemia in a Preterm Neonate with Ambiguous Genitalia: Two Generations Affected by Five Infant Deaths

Abstract

Propionic acidemia is a rare metabolic disorder caused by mutations in either the PCCB or PCCA gene, resulting in a deficiency of the propionyl-CoA carboxylase enzyme and the accumulation of its metabolites. It is a rare autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia. This case report describes a 45-day-old infant with failure to thrive and ambiguous genitalia presenting with respiratory distress, lethargy, recurrent vomiting, and poor weight gain. The family history revealed consanguinity (third-degree relatives) and the death of an older sibling at 35 days of age, who also had ambiguous genitalia, low birth weight, and prematurity. Additionally, three other infants in the previous generation had died. Arterial blood gas analysis showed elevated lactate levels with high anion gap metabolic acidosis. Ketonuria and hyperammonemia were also present. Tandem mass spectrometry–gas chromatography–mass spectrometry screening was done, which revealed increased propionyl-CoA metabolites. Whole exome sequencing further confirmed the diagnosis of propionic acidemia with autosomal recessive inheritance.