• Definition: inherited genetic disorders characterized by impaired metabolism of fats and proteins
• Pathophysiology
  • Propionic acidemia: propionyl-CoA carboxylase deficiency → impaired conversion of propionyl-CoA to methylmalonyl-CoA → ↑ propionyl-CoA and ↓ methylmalonate → conversion into propionic acid, which accumulates in serum and urine
  • Methylmalonic acidemia: methylmalonyl-CoA mutase deficiency or vitamin B12 deficiency → accumulation of methylmalonic acid
    • Methylmalonyl-CoA is transformed into succinyl-CoA by the enzyme methylmalonyl-CoA mutase, which requires adenosylcobalamin, the active form of vitamin B12, as a cofactor.
  • Accumulation of organic acids leads to
    • Urea cycle inhibition → hyperammonemia
    • Gluconeogenesis inhibition → hypoglycemia during fasting periods and increased risk of ketoacidosis (high anion gap metabolic acidosis)
• Clinical features
  • Most commonly present in infancy with poor feeding, vomiting, hypotonia, high anion gap metabolic acidosis, hepatomegaly, seizures.