In the Spring of 2025, I cared for the second child of a couple who ultimately died of “presumed” TRMU deficiency at 8 weeks of life. I knew this family well because I had cared for the couple’s older child about a year-and-a-half prior in November 2023 upon presenting with acute onset lactic acidosis and cardiomyopathy that resulted in an anion gap of >70 and death in the neonatal intensive care unit. In evaluating their older child in Fall of 2023, trio rapid genome sequencing from laboratory A was ordered and demonstrated a homozygous variant of uncertain significance (VUS) in TRMU (NM_018006.4:c.652-6_652-2del, splicing) with biparental inheritance, consistent with the clinical presentation and laboratory findings seen in TRMU deficiency.