Biochemical Basis of Heterogeneity in Acute Presentations of Propionic Acidemia

Abstract

Propionic acidemia (PA), an uncommon organic acidemia has varied clinical and metabolic presentation causing difficulty and delay in the diagnosis. We report a case of PA in an infant who presented with failure to thrive, acute encephalopathy due to severe hyperammonemia without acidosis and fungal sepsis. The biochemical basis of severe hyperammonemia is discussed.

A novel mutation in PCCB gene causing neonatal onset propionic acidaemia in a Sri Lankan patient

“…The biochemical defect is within the mitochondrial enzyme PCC, which converts propionic acid to methyl malonic acid using biotin as a cofactor 1,3 . Accumulated organic acid metabolites interfere with other metabolic pathways such as urea cycle, electron transport chain and glycine synthase complex resulting in lactic acidosis, hyperammonaemia, and ketotic hyperglycinaemia 4 .…”

“…High anion gap MA, elevated lactate, hyperammonaemia, elevated urinary ketone bodies are the biochemical hallmark of PA 4 . However, during the initial period, the accumulation of propionate and other metabolites may not be sufficient to cause MA 7 .…”

Novel mutation causing propionic acidemia associated with unexplained autoimmune thyrotoxicosis

“…Since several metabolic pathways are disrupted, propionic acidemia can be a diagnostic challenge because of the variety of biochemical abnormalities that may occur [ 6 ]. While propionate is a toxic metabolite in itself, when it is not converted to methylmalonyl CoA, the TCA cycle is disrupted leading to further impairment of energy production [ 1 ].…”

“…Mitochondrial disorders should be considered in cases of hyperammonemia, metabolic acidosis, ketonuria, and hypoglycemia [ 1 ]. Similarly, urea cycle disorders may also present with severe hyperammonemic encephalopathy without ketoacidosis [ 6 ]. A high glutamine level is usually seen in this group compared to the organic acidemias, although there may be an overlap [ 6 ].…”

“…They include poor feeding, vomiting and decreased activity with rapid progression towards encephalopathy that manifests as lethargy, seizures, or coma and can result in death [ 1 ]. This is frequently accompanied with severe ketoacidosis, hyperammonemia, and hyperglycinemia [ 1 , 6 ].…”