Methylmalonic Acidemia (MMA) is a metabolic disorder of methylmalonate and cobalamin metabolism. The signs and symptoms of this condition develop in early infancy. Infants present with vomiting, hypotonia, dehydration, lethargy, seizures, and failure to thrive. MMA is suspected in neonates with progressive encephalopathy along with severe metabolic acidosis, ketosis and ketonuria, hyperammonemia, hyperglycinemia, thrombocytopenia, and neutropenia.
Defects or absence of the Methylmalonyl-CoA Mutase (MCM) enzyme is the underlying cause in more than half of MMA cases. Mutations in MUT gene, which encodes MCM can lead to either complete enzyme deficiency [mut(0)], or partial enzyme deficiency [mut(-)].