Triosephosphate isomerase (TPI) deficiency was among the first human genetic disorders discovered by systematic enzymological screens more than 60 years ago.1 The syndrome is characterized by severe progressive neuromuscular degeneration (often manifesting as early as the first 7 months of life), neurologic dysfunction that is associated with impaired synaptic vesicle dynamics, hemolytic anemia and associated susceptibility to infections, and episodic hypotonia.2, 3, 4 Typically, patients are severely and systemically affected and do not reach the age of five. The gene discussed is TPI1; the disease is infection.