The methylmalonic acidemias are a family of disorders characterized by deficient activity of mitochondrial methylmalonyl-CoA mutase. This inborn error of organic acid metabolism leads to defects in organic acid, amino acid and lipid metabolism. Patients have a characteristic facies that includes a high forehead, broad nasal bridge and a long, smooth filtrum. Affected infants often have recurrence of acute illness with metabolic acidosis, vomiting, failure to thrive, lethargy, hypotonia, hepatomegaly, seizures and respiratory distress. The most severe clinical presentation is in the neonatal period and can result in death. The disorder may also have a later onset, in the first months or years or less commonly in early childhood. An adult form can have a benign course with a mild biochemical defect; however these individuals are at risk for acute metabolic decompensation. Complications of methylmalonic acidemia include mental retardation, nephritis, chronic renal tubular acidosis, metabolic stroke, pancreatitis, growth failure and functional immune impairment.