Propionic acidemia

Propionic acidemia (PA), also known as propionic aciduria or propionyl-CoA carboxylase deficiency, is a rare inherited metabolic disorder caused by deficiency of the mitochondrial enzyme propionyl-CoA carboxylase (PCC). This enzyme is essential for the breakdown of certain amino acids (isoleucine, valine, threonine, and methionine), odd-chain fatty acids, and cholesterol side chains. When PCC is deficient, propionic acid and other toxic metabolites accumulate in the body, leading to a wide range of serious health problems. The disease most commonly presents in the neonatal period with a life-threatening metabolic crisis characterized by poor feeding, vomiting, lethargy, hypotonia, and metabolic acidosis with an elevated anion gap. If untreated, this can rapidly progress to seizures, coma, and death. Chronic complications include developmental delay, intellectual disability, cardiomyopathy (a major cause of morbidity and mortality), recurrent metabolic decompensations triggered by illness or fasting, pancreatitis, bone marrow suppression (neutropenia, thrombocytopenia, pancytopenia), and movement disorders including dystonia and choreoathetosis. The central nervous system is particularly vulnerable, and basal ganglia injury can occur during metabolic crises. Management of propionic acidemia involves a combination of dietary restriction of propionic acid precursors (limiting natural protein intake with supplementation of propionic acid-free amino acid mixtures), carnitine supplementation to promote excretion of propionyl groups, and aggressive management of intercurrent illnesses to prevent metabolic decompensation. Metronidazole may be used intermittently to reduce propionate production by gut bacteria. Liver transplantation has been performed in severely affected patients and can reduce the frequency of metabolic crises, though it does not fully correct the metabolic defect in extrahepatic tissues and does not prevent cardiomyopathy. Cardiac transplantation has been necessary in some cases. Newborn screening via tandem mass spectrometry, detecting elevated propionylcarnitine (C3), enables early diagnosis and treatment initiation, which can improve outcomes.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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