General description

Propionic acidemia is an autosomal recessive metabolic disorder caused by mutations in the PCCA or PCCB genes, leading to deficient activity of propionyl-CoA carboxylase (PCC). This enzyme is critical for converting propionyl-CoA to methylmalonyl-CoA in the mitochondrial catabolism of branched-chain amino acids (isoleucine, valine, threonine, methionine) and odd-chain fatty acids. The resultant accumulation of propionyl-CoA and its toxic metabolites, including 3-hydroxypropionate, methylcitrate, and propionic acid, disrupts mitochondrial energy production, induces oxidative stress, and causes cellular damage across multiple organ systems.

Propionic acidemia can present in two main forms: neonatal-onset and late-onset or chronic progressive. In the neonatal form, symptoms appear soon after the first protein intake and include poor feeding, vomiting, low muscle tone, and rapid metabolic deterioration. Without early treatment such as protein restriction and medications to reduce ammonia levels, the condition can lead to seizures, coma, and death. Survivors often suffer from long-term complications like intellectual disability, movement disorders, and heart problems.

The late-onset form appears later in life, often during childhood or adulthood, and is usually triggered by stressors such as infections or high protein intake. It presents with acute brain dysfunction, involuntary movements, and psychiatric symptoms. The chronic progressive form involves persistent health issues such as poor growth, bone weakness, pancreas inflammation, and vision loss. A significant number of patients also develop heart problems, including abnormal heart rhythms and types of cardiomyopathy.

References

1. Brismar, Jan, and Pinar T. Ozand. "CT and MR of the brain in disorders of the propionate and methylmalonate metabolism." American journal of neuroradiology 15.8 (1994): 1459-1473.
2. Reddy, Nihaal, et al. "Neuroimaging findings of organic acidemias and aminoacidopathies." Radiographics 38.3 (2018): 912-931.