Sir,
Maple syrup urine disease (MSUD) is an autosomal recessive condition caused by a deficiency in the gene encoding the enzyme branched chain alpha ketoacid dehydrogenase (BCKDH), resulting in accumulation of branched chain amino acids (BCAAs) (leucine, isoleucine, valine) and their toxic byproducts. We present the perioperative anaesthesia challenges and management for liver transplantation in an infant with MSUD.
An 11-month-old male child (body weight 8 kg), a diagnosed case of MSUD, was referred to our institution for liver transplantation. On the 7th day after birth, the baby became lethargic, irritable, and was feeding poorly; he was admitted to another hospital. On day 15th of life, the baby was diagnosed with MSUD. After 2 months of strict MSUD diet, the child's condition and symptoms improved, except for three episodes of crisis-like situation which were managed conservatively with hydration, calorie supplementation, correction of metabolic abnormalities, and treatment of precipitating factors. The child also underwent dialysis once during one of these crisis episodes. During the crisis episodes, the leucine levels were found to be high (600–800 μmol/l), but decreased to <200 μmol/l after management. In view of good improvement on MSUD diet, he was advised liver transplantation. After a thorough preoperative workup and preanaesthetic evaluation, the child was posted for living donor-related liver transplantation, and the donor was his grandfather. Preoperative leucine levels were 418 μmol/l and valine was 468 μmol/l. Anaesthesia induction was as per the institutional protocol with fentanyl, propofol, and atracurium, followed by maintenance with isoflurane along with continuous infusions of atracurium and fentanyl. A 5.5-Fr. triple lumen catheter was inserted in the right internal jugular vein (ultrasound-guided), and left radial arterial cannula was placed. Ten grams of enteral MSUD formula was dissolved in 60 ml of saline and given at a rate of 10 ml/h via the nasogastric tube. Intralipid 20% was also administered as infusion. The surgery along with the reperfusion stage was uneventful. Electrolytes, lactate, and glucose levels were monitored with hourly arterial blood gas. He received a left lateral graft (282 g). The trachea was extubated on the table, and the child was shifted to the intensive care unit. His immunosuppressants were started on postoperative day 2 (POD2), and feed was started on POD3. His liver functions improved gradually, leucine levels normalized by POD6, and he was discharged from the hospital on POD19. The child has been stable over 2 years of follow-up, and enjoys an unrestricted diet.
The primary pathophysiology in MSUD is the accumulation of leucine in the plasma and organs, and severe metabolic decompensation is associated with the catabolism of tissue proteins at times of starvation and stress. Children are treated with dietary restriction of BCAAs and avoidance of catabolic states. Despite strict dietary control, severe metabolic crises can still develop during intercurrent illnesses and can be associated with life-threatening cerebral oedema. Due to a protein restricted diet, MSUD patients can also develop essential amino acid deficiencies, resulting in immunodeficiency, growth failure, and global developmental delays. Patients undergoing liver transplantation for MSUD should be carefully selected. Successful outcomes depend on a multidisciplinary approach to management in the perioperative period. Baseline levels of BCAAs should be noted, and if found excessive, transplantation should be deferred and medical treatment initiated. Patients with MSUD cannot be fasted without catabolic consequence, and specialized total parenteral nutrition should be used that include concentrated dextrose infusions. It is essential, to avoid metabolic decompensation, that plasma BCAAs are within target ranges and dehydration and acidosis corrected before taking up the child for transplantation. Lipid infusion provides calories without causing overhydration and haemodilution, preventing cerebral oedema and death that have been reported previously in catabolic states. Perioperative sedation and analgesia should be optimized to avoid catabolism, and physiologic stress should be kept to a minimum. In our case, the child is under regular follow-up for 2 years, and has been leading a normal healthy life with unrestricted diet intake. The development of liver transplantation as a treatment for MSUD has dramatically improved the quality of life in these patients. In conclusion, we can say that MSUD, being a rare genetic disease, presents a unique set of perioperative challenges for the anaesthesiologist.[1234]
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The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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