Background/Objectives: 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) is an extremely rare autosomal recessive metabolic disorder caused by mutations in the HMGCL gene. HMGCLD disrupts ketogenesis and β-oxidation, leading to energy failure during fasting or stress, with clinical episodes characterized by hypoglycemia, hyperammonemia, lactic acidosis, and encephalopathy. Only 211 cases have been reported worldwide, with no prior reports on anesthetic management in these patients. Clinical features: We report a 14.5-year-old girl with known HMGCLD who was admitted with abdominal pain and nausea following a fatty meal. Imaging confirmed acute cholecystitis. Initial conservative management failed due to persistent vomiting and inability to tolerate feeding. Deviation from the metabolic protocol led to lactic acidosis and hypoglycemia, requiring intensive care with bicarbonate, carnitine, and glucose infusion. Once optimized, she underwent emergency laparoscopic cholecystectomy under sevoflurane-based anesthesia. Propofol was avoided given the patient’s compromised lipid metabolism. Intraoperative glucose and acid-base status were closely monitored, with balanced dextrose-based fluids. The patient remained hemodynamically stable throughout and was discharged three days postoperatively. Conclusions: This case highlights the anesthetic challenges of HMGCLD, where system-level miscommunication can trigger severe metabolic decompensation. A review of the literature emphasizes fasting avoidance, continuous glucose supplementation, careful drug and fluid selection, and multidisciplinary coordination. This report provides the first anesthetic roadmap for HMGCLD, underscoring the need for individualized care and meticulous perioperative metabolic control.

Background/Objectives: 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) is an extremely rare autosomal recessive metabolic disorder caused by mutations in the HMGCL gene. HMGCLD disrupts ketogenesis and β-oxidation, leading to energy failure during fasting or stress, with clinical episodes characterized by hypoglycemia, hyperammonemia, lactic acidosis, and encephalopathy. Only 211 cases have been reported worldwide, with no prior reports on anesthetic management in these patients. Methods: We report a 14.5-year-old girl with known HMGCLD who was admitted with abdominal pain and nausea following a fatty meal. Imaging confirmed acute cholecystitis. Initial conservative management failed due to persistent vomiting and inability to tolerate feeding. Deviation from the metabolic protocol led to lactic acidosis and hypoglycemia, requiring intensive care with bicarbonate, carnitine, and glucose infusion. Once optimized, she underwent emergency laparoscopic cholecystectomy under sevoflurane-based anesthesia. Propofol was avoided, given the patient’s compromised lipid metabolism. Intraoperative glucose and acid-base status were closely monitored, with balanced dextrose-based fluids. Results: The patient remained hemodynamically stable throughout and was discharged three days postoperatively. Conclusions: This case highlights the anesthetic challenges of HMGCLD, where system-level miscommunication can trigger severe metabolic decompensation. A review of the literature emphasizes fasting avoidance, continuous glucose supplementation, careful drug and fluid selection, and multidisciplinary coordination. This report provides the first anesthetic roadmap for HMGCLD, underscoring the need for individualized care and meticulous perioperative metabolic control.