Asparaginase is well recognized as a crucial element in the treatment of pediatric acute lymphoblastic leukemias (ALL).¹ It is an enzyme that exerts its anti-leukemic effects by catalyzing the breakdown of asparagine to aspartic acid and ammonia.¹The E. coli -derived asparaginase formulations, L-asparaginase and pegaspargase, have high rates of antibody development that can ultimately lead to inadequate asparaginase activity.²To combat this, Erwinia chrysanthemi -derived asparaginase was developed, of which several products exist: conventional Erwinia asparaginase (Erwinaze), and, the newest formulation, recombinant Erwinia asparaginase (Rylaze).^2,3

As ammonia is a byproduct of asparaginase’s mechanism, acute, transient hyperammonemia is expected.^4,5 Symptomatic hyperammonemia may present as headache, nausea, vomiting, lethargy, or in severe cases, encephalopathy, coma, or death.^6–8There are several case reports describing symptomatic hyperammonemia in patients receiving pegaspargase and conventional Erwinia asparaginase, but herein we describe two patients who developed symptomatic hyperammonemia secondary to recombinant Erwinia asparaginase.^6,9,10