Dysfunction of oxidative phosphorylation and the mitochondrial respiratory chain leads to a heterogeneous group of pathogenic mitochondrial variations. The TRMU gene codes for transfer RNA 5-methylaminomethyl-2-thiouridylate methyltransferase and is essential for posttranscriptional modification of the mitochondrial transfer RNA, and alterations in the TRMU gene can lead to infantile liver failure at approximately 6 months of age. Orthotopic liver transplant is a curative option. We present a case of a patient with TRMU alteration who underwent liver transplant at 11 months of age to treat infantile end-stage liver disease. The patient had liver failure due to long-standing allograft rejection and required another liver transplant at age 24 years, and here we discuss the perioperative care of this patient. Coordination of the care team to prevent rhabdomyolysis or alternative negative catabolic effects was the cornerstone of management in addition to evaluation of unusual electrocardiographic findings in the immediate postoperative period. Although the patient’s postoperative course was complicated by repair of a bile leak, liver retransplant successfully restored the patient’s preoperative quality of life.

Key words : Liver transplant, Mitochondrial disease, Perioperative care, TRMU alteration

Introduction

Mitochondrial disorders comprise a group of diseases caused by defective mechanisms in oxidative phosphorylation and the electron transport chain. An essential element of mitochondrial function is encoded by the TRMU gene, which codes for transfer RNA 5-methylaminomethyl-2-thiouridylate methyltrans-ferase (TRMU), a protein involved in mitochondrial DNA translation.¹ A patient with a TRMU alteration may present with hypoglycemia, increased lactate level, developmental delays, and liver failure. Spontaneous recovery has been described, but serious manifestations may necessitate orthotopic liver transplant when the patient is relatively young. We present a case of a 24-year-old man with a history of TRMU alteration who underwent liver transplant in infancy and had end-stage liver disease due to chronic allograft rejection. Perioperative manage-ment required coordination of the team in the postanesthesia care unit (PACU) to prevent fasting catabolism and to address recurrent unexpected abnormalities in the electrocardiogram results.

Case Report

A 24-year-old man presented with worsening generalized weakness, abdominal pain, nausea, and chills. He was admitted for acute kidney injury and partial obstruction of the small bowel. His past medical history included acute infantile liver failure due to a TRMU alteration. As a result, he underwent split liver transplant at the age of 11 months. Subsequently, he had chronic allograft rejection with cirrhosis, hepatic encephalopathy, and spontaneous bacterial peritonitis. With the TRMU alteration, the patient had contraindications to acetaminophen, amide local anesthetics, lactated Ringer solution, and aminoglycosides. A nasogastric tube was placed to decompress the small bowel. Midodrine and subcutaneous octreotide were administered for hepatorenal syndrome. Glucose-containing solutions were administered without interruption throughout the admission process to prevent catabolism and rhabdomyolysis.

On day 4 of hospitalization, the patient under-went liver transplant with the piggyback technique and an allograft from a deceased donor after brain death. During surgery the patient received 8 U fresh frozen plasma, 5 U pooled platelets, 9 U packed red blood cells, 2275 mL autologous red blood cell salvage, and 4 U pooled donor cryoprecipitate. Emergence from anesthesia and extubation occurred immediately after surgical closure. Thirty minutes after the patient arrived in the PACU, ST-segment elevation appeared on telemetry in leads V₄, V₅, and V₆. Despite the ST-segment elevation, other vital signs were unremarkable, and the patient was asymptomatic. Laboratory analysis showed mildly elevated troponin levels, which prompted consul-tation with a cardiologist, who suspected pericarditis and ruled out acute coronary syndrome. Follow-up echocardiography showed normal results for wall motion and ejection fraction.

The patient’s postoperative course was then complicated by a bile leak that required general anesthesia for drain placement by an interventional radiologist. In the PACU, echocardiography again showed ST-segment elevation in leads V₄, V₅, and V₆. The troponin level was elevated, and results of bedside echocardiography were unremarkable. A presumptive diagnosis of pericarditis was reaffirmed by a cardiologist during an urgent consultation. After the pericarditis resolved, the patient’s preoperative quality of life was restored.

Discussion

Long-term outcomes for patients with TRMU alteration can vary from full recovery to death due to liver failure or heart failure, although data are limited. Early L-cysteine supplementation can prevent the need for orthotopic liver transplant.² Patients remain susceptible to rhabdomyolysis with catabolic stress, including fasting. In general, patients with inherited mitochondrial diseases are more susceptible to adverse effects from anesthetic agents than the general population. Use of succinylcholine should be avoided to prevent hypokalemia, and propofol by bolus, rather than continuous administration, is preferred, to avoid toxicity. Patients with mitochondrial disease often have increased levels of lactate, so solutions without lactate are preferred for volume resuscitation. Successful postoperative care for these patients requires continuous dextrose supplementation with monitoring for hyperglycemia and lactic acidosis.³

This case presented a multifactorial challenge to the care team. The patient had a past medical history of a rare metabolic disorder in combination with unexpected abnormal electrocardiographic findings after liver retransplant. Incidence of mitochondrial disease is rare, and so there is presently no established comprehensive set of expectations to guide clinicians with perioperative management of these cases.

References:

1. Gaignard P, Gonzales E, Ackermann O, et al. Mitochondrial infantile liver disease due to TRMU gene mutations: three new cases. JIMD Rep. 2013;11:117-123. doi:10.1007/8904_2013_230
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2. Murali CN, Soler-Alfonso C, Loomes KM, et al. TRMU deficiency: a broad clinical spectrum responsive to cysteine supplementation. Mol Genet Metab. 2021;132(2):146-153. doi:10.1016/j.ymgme.2021.01.005
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3. Mitochondrial Medicine Society’s Committee on Diagnosis, Haas RH, Parikh S, et al. The in-depth evaluation of suspected mitochondrial disease. Mol Genet Metab. 2008;94(1):16-37. doi:10.1016/j.ymgme.2007.11.018
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