Dear Editor:

Maple syrup urine disease (MSUD), an inherited autosomal recessive disorder of branched-chain amino acid metabolism, is characterized by potentially life-threatening episodes of ketoacidosis.^1,2 Leucine, isoleucine, and valine also are neurotoxic, and long-term high levels can produce different grades of neurologic impairment if the disease is not treated.³ Patients would need to follow a special diet with exclusion of branched amino acids their entire life. The failure to control diet leads to the development of deficits, and the urine’s particular aspect, which leads to the name of the disease. Aside from early control of diet, another therapy could be a liver transplant, which provides enough volume of enzymes, offering the patient a chance of a normal diet and the ability to stop progression of the disease. While the liver has otherwise normal functioning, the concept of transplanting MSUD patient’s liver, as a domino liver transplant, to a patient without the disease, where the muscles and kidney cover the metabolic needs, becomes a reality in practice. Herein, we report the first case of a domino liver transplant done in Saudi Arabia for MSUD.

A 12-year-old, 33 kg patient, with MSUD was evaluated, and a liver transplant was indicated, planning to use his native liver as a domino liver transplant. He was diagnosed as having MSUD since birth, with a history of seizures and encephalitis 40 days after birth. He developed fine and gross motor dysfunction. He had good brain function, good performance in practical reasoning, speech, and language; however, there was a delay in his personal skills, hand coordination, and performance skills owing to spasticity in his hands. The second recipient was a 55-year-old, 61-kg female patient with HCV cirrhosis and HCC under Milan criteria, after transarterial chemoembolization. A 6-year-old brain dead donor secondary to a head trauma, with a body weight of 20 kg became available, and the decision to proceed with the transplant was taken. After recovering the 380-gram liver graft has a replaced right hepatic artery coming from the superior mesenteric artery, so the proximal abdominal and the thoracic aorta were recovered en bloc with the celiac and the superior mesenteric artery. The child with MSUD had a hepatectomy, which was done with the preservation of the native inferior vena cava, and the transplant was performed in a piggyback fashion. The portal vein was anastomosed end-to-end, and the arterial supply was re-established using the thoracic aorta of the donor as a jump graft to infrarenal aorta. The biliary anastomosis was duct-to-duct. The second recipient received a modified piggyback technique. The graft weight was 564 grams, and it had 2 arteries—the right and a replaced left, originating from left gastric artery. Portal vein anastomosis was also done end-to-end. The arterial anastomoses were done under a microscope using the native right and left hepatic arterial stumps. The biliary anastomosis was duct-to-duct.

The pediatric recipient was extubated on postoperative day (POD) 1 and was transferred to the ward on POD 4 and started on special formula on POD 5. As immunosuppression, he was given basiliximab induction intraoperatively and started on tacrolimus on POD 3. His evolution was favorable, but on POD 19 he presented abdominal pain, distention, and vomiting. A clinical examination revealed an acute abdomen, and the computed tomographic scan showed a dilated bowel with free intra-abdominal fluid. An exploratory laparotomy identified a small perforation in the early segment of jejunum, which was primarily repaired. After that he had an uneventful hospital course and was discharged on POD 28. Plasma levels of his branched-chain amino acids and alloisoleucine were within the normal parameters by POD 20.

The adult recipient of the MSUD graft had an eventful postoperative course, being extubated on POD 2 and started on an oral diet on POD 3. As an immunosuppressant, she was given basiliximab induction intraoperatively and was started on tacrolimus on POD 4 and mycophenolate mofetil on POD 5. She was discharged on POD 12.

Up until the end of 2015, in the United States, 214 domino liver transplants were performed with the first case reported in 1996.4 Maple syrup urine disease grafts are safe to use in patients with a normal enzymatic profile with good outcomes and no dietary restrictions for recipients.^2,5

In one of the largest series published to date, the results for liver transplant recipients with MSUD are excellent, with patient and graft survival of 100% at 4.5 years, with the patient on a normal nonrestrictive diet. The neurologic impairment stops soon after the transplant, but the intelligence quotient shows no statistical significant improvement over time.6 Even so, the liver is the source of only 9% of the enzymatic complex brain chained alpha-ketoacid dehydro­genase, which is involved in the patho­genesis of the disease; therefore using a smaller graft from a living donor is also safe for the patients.⁷

In conclusion, we present the first case of a domino liver transplant performed in Saudi Arabia. A liver transplant is an effective treatment for patients with MSUD. Using a liver graft from these patients is an effective and valuable resource for organs from other patients on the transplant wait list.

References:

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3. Strauss KA, Wardley B, Robinson D, et al. Classical maple syrup urine disease and brain development: Principles of management and formula design. Mol Genet Metab. 2010; 99(4): 333-345.
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4. UNOS transplant data. https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/
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